Divergent Construction of Thiochromanes and N-Arylbutanamides via Arylthiodifluoromethyl Radical-Triggered Cascade of Alkenes.

A strategy utilizing silver-catalyzed oxidative decarboxylation radical cascade cyclization of arylthiodifluoroacetic acids with alkenes for the simple and efficient preparation of difluoromethylated thiochromanes and 2,2-disubstituted-N-arylbutanamides derivatives has been developed. This approach includes good functional group tolerance, easily accessible starting materials, and operational simplicity.

miR-212 as potential biomarker suppresses the proliferation of gastric cancer via targeting SOX4.

BACKGROUND: Circulating microRNAs that post-transcriptionally regulate gene expressions have been reported as promising biomarkers in cancer monitoring. This study was to identify the potential role of circulating miR-212 in gastric cancer and whether it could serve as a novel biomarker for gastric cancer. METHODS: We detected the serum levels of miR-212 in 100 health people and 110 gastric cancer patients and analyzed the relationships of the serum level of miR-212 with gastric cancer. We detected the expression of miR-212 in human gastric mucosal epithelial cell line (GES-1) and human gastric cancer cell lines (NCI-N87 and SNU-16) using qRT-PCR. Then, we detected the role of 5-aza-deoxycytidine on the epigenetic regulation of miR-212 in human gastric cancer cell lines. Furthermore, luciferase reporter assay was used to detect binding activity of miR-212 on SOX4 mRNA, and their functions on the cell proliferation and apoptosis. RESULTS: The expression of miR-212 was higher in health people than that in gastric cancer patients, higher in gastric mucosal epithelial cell line than that in gastric cancer cells. miR-212 can be a circulating biomarker and an independent prognostic factor of gastric cancer. Moreover, miR-212 can directly regulate the 3'UTR of SOX4 mRNA to suppress p53 and Bax, resulting gastric cancer cells proliferation inhibition and apoptosis induction. CONCLUSION: Our study demonstrated that miR-212 was epigenetically downregulated in gastric cancer, and resulting low level of miR-212 can be a potential circulating biomarker and poor prognosis predicator of gastric cancer.

miR-519d-3p Inhibits Cell Proliferation and Invasion of Gastric Cancer by Downregulating B-Cell Lymphoma 6.

miR-519d inhibits cell growth, migration, and invasion, but its role in gastric cancer (GC) cells is obscure. We showed that miR-519d-3p was lowly expressed in GC tissues and was associated with the clinical stage and lymph node metastasis of GC tissues. We found that miR-519d-3p repressed cell proliferation and invasion of MGC803 cells and delayed the G1/S phase transition, resulting in decreased cyclin B1 and MMP2 and increased E-cadherin levels. Furthermore, miR-519d-3p targeted and downregulated B-cell lymphoma 6 (BCL6) expression. BCL6 overexpression partially abrogated the suppressive function of miR-519d in MGC803 cells. In conclusion, our study demonstrated that miR-519d-3p functions as a tumor suppressor by targeting and downregulating the expression of BCL6 in GC cells.

Inhibitory effects of baicalin on orthotopic xenografts of colorectal cancer cells that are deficient in a mismatch repair gene in nude mice.

OBJECTIVE: The aim of this article is to study the inhibitory effects of baicalin on the growth and metastasis of orthotopic xenografts consisting of human HCT-116 colorectal cancer cells that are deficient in the mismatch repair gene hMLH1 in nude mice. METHODS: A fluorescent orthotopic transplantation model of HCT-116 cells was established. The treatment groups were administered baicalin 50 mg/kg (G2), 100 mg/kg (G3), and 200 mg/kg (G4), and the negative control group (G1) was administered 5 % NaHCO3. The volume and vascular density of the primary tumors, body weights, survival conditions, and death rates of the mice were analyzed. RESULTS: On the 14th, 21st, and 28th days, tumor volume in the treatment groups was significantly smaller than that in the control group, and the differences were statistically significant. At the end of the experiment, the survival rate of the experimental animals in the G3 was significantly higher than that in the G1 and G4 (P < 0.05). There were no significant differences in both the weights and surface vascular densities of the primary tumor and the metastatic tumor among all groups. CONCLUSION: Baicalin had a significant inhibitory effect on the growth of nude mouse orthotopic xenografts consisting of human HCT-116 colorectal tumor cells that are deficient in the mismatch repair gene hMLH1.

[Effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer].

OBJECTIVE: To study the anticancer effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer. METHODS: Sixty orthotopic transplantation mice model of human colon cancer cell line HCT-116 expressing eGFP were established, which were divided randomly into negative controlled group (5% NaHCO3) and 50, 100, 200 mg/kg Baicalin groups. The nude mice were treated with intragastric infusion twice a day. Nude mice growth state, average weigh, inhibition rate of transplanted tumor, tumor metastasis and survival state were observed. RESULTS: At 14, 21 and 28 days after treatment with different dose of Baicalin, tumor growth velocity was significantly slower in the treatment groups, and tumor volume was significantly smaller than the controlled group (there were (832 ± 637), (2012 ± 1566) and (2494 ± 1557) mm(3) respectively in 14, 21 and 28 days) (F = 4.433, P < 0.05). At the end point of study, survival state of 100 mg/kg group (13/15) was superior to controlled group (8/15) and 200 mg/kg group (8/15) (χ(2) = 4.665 and 3.980, P < 0.05).However, there were no significant differences in tumor metastasis and tumor surface vessel density. CONCLUSIONS: Baicalin has statistically significant effects in inhibiting tumor growth in an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer, and 100 mg/kg may be an ideal treatment dose.

Glomangiomatosis - immunohistochemical study: A case report.

BACKGROUND: Glomangiomatosis (also known as diffuse glomus tumor) is extremely rare, accounting for only 5% of glomus tumors. The prevalence of glomus tumors is only 2% of soft tissue tumors. Lesions can recur after resection. Although growth may be diffuse or infiltrating and invasive, definitive identifying standards for malignant glomus tumors are lacking. This article describes a case of glomangiomatosis with many nodular masses in the soft tissues of the right foot and calf. A review of the Chinese and English-language literature is included. CASE SUMMARY: A case of glomangiomatosis in a 55-year-old Chinese woman who presented clinically with many nodular masses in the soft tissues of the right foot and calf. The tumor was examined histologically and immunostaining was performed. CONCLUSION: Glomangiomatosis occurs most often in young people, in the distal extremities, but is rare. Multiple nodules are even rarer. Only 15 clinicopathological analyses of glomangiomatosis have been reported in the combined Chinese- and English-language literature. In the present case, microscopically, nested vascular globular cells were observed around the blood vessel wall. Immunohistochemistry revealed diffuse immunoreactivity for smooth muscle actin, vimentin, type IV collagen, and Bcl-2. Caldesmon, CD34, and calponin were weakly, partially, and slightly positive, respectively. There was no recurrence 1 year after resection.

Uterus-like mass in the right broad ligament: A case report.

RATIONALE: Uterus-like masses (ULMs) are rare benign lesions that resemble the uterus. PATIENT CONCERNS: Here, we describe the case of a woman with a ULM in the right broad ligament. A 51-year-old woman with a 2-month history of irregular vaginal bleeding was found to have a mass in the right broad ligament. Imaging studies revealed a solid-cystic lesion, suggestive of an endometrial cyst with malignant transformation. INTERVENTIONS: She underwent prompt surgery for the removal of the mass. Intraoperatively, the uterus and ovaries appeared normal, and an 8-cm-long mass was observed in the right broad ligament without any connection to the uterus or ovaries. The mass was successfully excised. DIAGNOSES: Postoperative histopathological examination showed that the cystic mass was filled with a blackish-brownish fluid and that it had thick walls resembling the uterine myometrium. The cyst center was lined by endometrial glands that were positive for cytokeratin as well as estrogen and progesterone receptors, and by stromal cells that were positive for CD10. OUTCOMES: The patient recovered well and has had no further symptoms during 2 years of follow-up. LESSONS: We have reported a case of ULM in the right broad ligament in a Chinese woman. Although ULMs are rare, they should be considered in the differential diagnosis for pelvic masses.

Detection of JAK2 V617F mutation increases the diagnosis of myeloproliferative neoplasms.

The Janus kinase (JAK)2 gene, which is located on chromosome 9p24, is involved in the signaling transduction pathways of the hematopoietic and immune system. Mutations in the JAK2 gene have served as disease markers for myeloproliferative neoplasms (MPNs). The aim of the present study was to investigate the occurrence of the JAK2 gene mutation in 140 clinical samples, and to evaluate its clinical significance in MPNs and other hematological diseases. Genomic DNA was extracted from the peripheral blood leukocytes or bone marrow karyocytes of 140 clinical samples, which included 130 patients with various types of hematological disease and 10 control patients. In addition, exons 12 and 14 of the JAK2 gene were analyzed by direct sequencing and the mutation rates of various MPN subtypes were evaluated. Of the 140 samples, exons 12 and 14 were tested in 74 samples, however, exon 14 only was tested in 66 samples. No mutations were identified in exon 12. The V617F mutation rate in polycythemia vera was 82.1% (23/28), and the mutation rates in essential thrombocythemia histiocytosis, primary myelofibrosis and other MPNs were 53.1% (17/32), 40.0% (4/10) and 60.0% (6/10), respectively. Therefore, the total mutation rate of the JAK2 gene in MPN was 62.5% (50/80). For non-MPN hematological diseases, four V617F mutations were detected in samples of leukocytosis of unknown origin (4/12), however, no JAK2 V617F mutations were identified in the 10 controls. Therefore, JAK2 V617F mutations may present a novel marker for diagnosis of MPNs. Furthermore, the direct sequencing method appeared to be satisfactory for the clinical gene testing of hematological samples.

A GFP-labeled human colon cancer metastasis model featuring surgical orthotopic implantation.

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP- labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

BAT-25 polymorphism in Chinese from Jiangsu province and its implication for locus microsatellite instability screening.

BACKGROUND: Colorectal cancer is one of the most common tumors with high mortality in China. Microsatellite instability (MSI) analysis is important for the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) and for the prediction of 5-FU chemotherapy efficiency of colorectal tumors, especially in terms of therapeutic response and overall survival rates. Among the MSI markers recommended by the NIH/NCI, BAT-25 has been extensively studied for its major role in MSI. BAT-25 presents different polymorphisms in different ethnic populations and studies of its polymorphisms in the Chinese population are still very limited. AIMS: To analyze the frequency of constitutive polymorphic variation at the BAT-25 locus in Chinese from Jiangsu Province and its implication for locus MSI screening. METHODS: The frequency of allelic variation at the BAT-25 locus of cervical cells from 500 healthy women and blood from 16 healthy males was assessed by direct sequencing. Twenty samples were also analyzed by fragment analysis. DNA extracted from blood of 94 patients with gastrointestinal cancer or endometrial cancer was analyzed by fragment analysis. RESULTS: After comparison with the sequencing results, the more frequent allele lengths were 126-127 bp, 128-129 bp, 129-130 bp, respectively consistent with the 24 poly(T) (T24), T25 and T26 alleles. At the BAT-25 locus, 516 healthy individuals had respectively 1.36%, 97.28% and 1.36% of the T24, T25 and T26. Whereas for the 94 cancer patients allelic frequencies were 0.53%, 1.06%, 96.8%, 1.6% for T15, T24, T25 and T26 alleles respectively. Sixteen healthy males had only the T25 allele and heterozygous T15 was only found in 1 male patient with colon cancer. CONCLUSION: We established the relation between fragment length and thymine repeats in BAT-25. The results showed that the BAT-25 locus is quasimonomorphic in Chinese from Jiangsu province. Moreover we showed that variant alleles of BAT-25 were found more likely in blood from cancer patients than in healthy individuals, suggesting the need to perform comparative studies between tumor and blood, or normal tissue, as to obtain a correct MSI identification.