Suspected coexistence of perianal necrotizing sweet syndrome in chronic myelomonocytic leukemia: A case report.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) complicated with Sweet syndrome (SS) is a rare hematological neoplasm. However, cases of concomitant development of perianal necrotizing SS (NSS) have not been reported. CASE SUMMARY: We report a case of a 49-year-old male patient who underwent sequential procedures for hemorrhoids and perianal abscess. He developed postoperative incision infection and was referred to the department where the authors work. Initially, perianal necrotizing fasciitis secondary to incision infection after perianal abscess surgery was suspected. Despite receiving antibiotic therapy and undergoing surgical debridement, deeper necrotic areas formed in the patient's perianal wounds, accompanied by persistent high fever. Blood and fungal cultures yielded negative results. The final diagnosis was corrected to be CMML with suspected concomitant perianal NSS. CONCLUSION: CMML with perianal NSS is a rare condition, often misdiagnosed as perianal abscess or perianal necrotizing fasciitis. Conventional antibiotic therapy and surgical debridement are ineffective in managing this condition.

Antiproliferative and Anti-inflammatory Withanolides from Physalis angulata.

Sixteen new withanolides, physangulatins A-N (1-14) and withaphysalins Y and Z (15 and 16), as well as 12 known analogues, were isolated from the stems and leaves of Physalis angulata L. Their structures were established using extensive spectroscopic data analyses. The absolute configurations of 1 and 9 were assigned via X-ray crystallography. The isolated compounds were tested for their antiproliferative effects against human prostate cancer cells (C4-2B and 22Rvl), human renal carcinoma cells (786-O, A-498, and ACHN), and human melanoma cells (A375-S2), as well as inhibitory effects on NO production induced by LPS in macrophages. Compounds 9, 17, 20, 21, 25, and 27 showed antiproliferative effects against all tested cancer cells, with IC50 values of 0.18-7.43 µM. Compounds 3-5, 9-11, 17, 20-22, 24, 25, and 27 displayed inhibitory effects against NO production, with IC50 values of 1.36-11.59 µM.

Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense.

Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26µM.

Berberine induces apoptosis and DNA damage in MG­63 human osteosarcoma cells.

Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, has been found to exhibit marked anticancer effects on a panel of established cancer cells. Among the human osteosarcoma lines treated, MG­63 cells were found to be the most sensitive. The present study investigated the potential genotoxic effect of berberine on MG­63 human osteosarcoma cells. The effect of berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5­diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow cytometry and a DNA ladder assay. γH2AX focus formation was used to detect DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis in MG-63 cells in a concentration- and time-dependent manner, as determined by DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control. In conclusion, these observations indicated that berberine induced apoptosis and DNA damage in MG­63 cells.

Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1.

The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression.

Insertion/deletion (I/D) in the angiotensin-converting enzyme gene and breast cancer risk: lack of association in a meta- analysis.

PURPOSE: Breast cancer is an important cause of cancer-related death in women. Numerous studies have evaluated the association between the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and breast cancer risk. However, the specific association is still controversial rather than conclusive. Therefore, we performed a meta-analysis of related studies to address this controversy. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between the I/D polymorphism in the ACE gene and susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: 10 separate studies of 7 included articles with 10,888 subjects on the relation between the I/D polymorphism in the ACE gene and breast cancer were analyzed by meta-analysis, and our results showed no association between the I/D polymorphism in the ACE gene and breast cancer in total population and different populations. No publication bias was found in the present study. CONCLUSIONS: The ACE I/D polymorphism may not be associated with breast cancer risk. Further large and well-designed studies are needed to confirm this conclusion.

PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase.

Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5' untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance.

[Quantity and distribution of CD44+/CD24- cells in breast cancer tissue and the cell lines].

OBJECTIVE: To study the distribution and quantity of CD44+/CD24- cells in breast cancer tissue and the cell lines, and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma. METHODS: The expression of CD44/CD24, estrogen receptor, progesterone receptor, HER2, human estrogen-induced protein PS2, bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining. The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) was also examined. RESULTS: The quantity and distribution of CD44+/CD24- cells varied greatly and no specific patterns were identified. The percentage of CD44+/CD24- in breast cancer was 65%. The amount of CD44+/CD24- cells did not correlate with the age of patients, lymph node metastasis, tumor size, molecular subtypes and expression of various breast cancer markers in breast carcinoma. The proportion of CD44+/CD24- cells in MCF-7, MDA-MB-468, and MDA-MB-231 cell lines was <1%, 5% and >80%, respectively. CONCLUSIONS: CD44+/CD24- cells are demonstrated in certain breast cancer tissues and cell lines. However, there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer.

[Hydroa vacciniforme-like cutaneous T cell lymphoma: a case report and literature review].

OBJECTIVE: To study the clinical features, diagnosis and therapy of hydroa vacciniforme-like cutaneous T cell lymphoma. METHODS: The clinical presentations and the findings of laboratory examinations and skin biopsy of affected tissue in a child with hydroa vacciniforme-like cutaneous T cell lymphoma were retrospectively reviewed. RESULTS: The child manifested as rash, fever and lymph node intumesce. Rash was pantomorphia, including edematous erythema, vesicles, crusts, necrosis and depressed scar, and it was mild in winter and severe in summer, mainly involving in the face and extremities. Epstein-Barre virus (EBV)-IgM was positive. Histopathological findings revealed focal lymphocyte invasion in subcutaneous panniculus adiposus, mainly surrounding the blood vessels. Immunohistochemistry showed CD3 (+), CD43 (+), CD20 (-), pax-5 (-), TIA (+), CD5 (+), CD8 (+), Granmye (+) and CD4 (-). The clinical symptoms were improved after glucocorticoid treatment in this child. CONCLUSIONS: Hydroa vacciniforme-like cutaneous T cell lymphoma has special clinical manifestations. This disorder may be definitely diagnosed by skin biopsy of affected tissue and immunohistochemistry assay. Glucocorticoid treatment is effective. EBV infection may be related to the development of this disorder.

[Effect of nanosize delivery system for ASODN against hTERT on the expression of telomerase in the esophageal cancer EC9706 cells].

OBJECTIVE: To investigate the inhibitory effect of nanoparticle-mediated antisense oligodeoxynucleotide (ASODN) of human telomerase reverse transcriptase (hTERT) on telomerase in the esophageal cancer EC9706 cells. METHODS: Line-polyethylenimine (L-PEI) was used to condense ASODN into nanoparticle and to couple NGR peptides into targeting nanoparticle, and the prepared L-PEI/ASODN complexes were transfected into the EC9706 cells. Cellular uptake of L-PEI/ASODN complexes was detected by laser confocal scanning microscopy. MTT assay was used to detect the inhibitory rate of EC9706 cell growth. The level of hTERT mRNA and its protein expression were measured by RT-PCR and immunohistochemistry, respectively. Annexin V FITC/PI double labeling was used to detect cell apoptosis. The distribution of drug in nude mice was observed by laser confocal scanning microscopy, and the growth and morphology of the tumor was examined. RESULTS: The L-PEI-mediated ASODN uptake was enhanced. After transfection, the inhibitory rate of EC9706 cells was time-dependant and there was a significant difference between control cell group and L-PEI/ASODN group (P < 0.05). At 48 h after transfection, the level of hTERT mRNA was decreased significantly compared with that of control cell group (P < 0.05), and the expression of hTERT protein was negative. There was apparent apoptosis in EC9706 cells after transfection with L-PEI/ASODN complexes. For the two NGR/L-PEI/ASODN groups, fluorescence was observed in the liver, kidney, lung and tumor tissues of nude mice, and their uptake intensity was time-dependent. The mean volume of tumors in the two NGR/L-PEI/ASODN groups was significantly smaller than those in blank control group and SODN group (P < 0.05). Apoptotic bodies were detected in the tumors of L-PEI/ASODN group. CONCLUSION: The NGR/L-PEI/ASODN nanoparticles can effectively reach into the human esophageal cancer xenograft and inhibit the tumor growth in nude mice, and this may provide a theoretical and experimental basis for gene therapy for human esophageal squamous cell carcinoma.

Expression of phosphatase of regenerating liver 1 and 3 mRNA in esophageal squamous cell carcinoma.

CONTEXT: Phosphatase of regenerating liver (PRL) 3 messenger RNA (mRNA) was reported to express in human colorectal, gastric, ovarian, breast, and hepatic cancers. OBJECTIVE: To examine the expression of PRL-1 and PRL-3 mRNAs in human esophageal squamous cell carcinoma (ESCC). DESIGN: Expression of PRL-1 and PRL-3 mRNA was examined with reverse transcriptase-polymerase chain reaction in fresh tissue collected from 40 cases of ESCC with matched lymph node metastasis in 21 cases. The association of expression of PRL-1 and PRL-3 mRNAs with clinicopathologic parameters was analyzed. RESULTS: The frequencies of PRL-1 and PRL-3 mRNA expression were significantly higher in ESCC than in normal esophageal tissue (P = .001; P = .01) and also significantly higher in ESCC with lymph node metastasis than in those without lymph node metastasis (P = .01; P = .03). The levels of PRL-1 and PRL-3 mRNA expression were significantly higher in ESCC with lymph node metastasis than in those without lymph node metastasis (P = .04; P = .04). The frequencies and levels of PRL-1 and PRL-3 mRNA expression were correlated with the later stages but not with tumor differentiation, tumor location in the esophagus, patient's sex, and age. CONCLUSIONS: PRL-1 and PRL-3 mRNAs may be involved in and used to predict the metastasis of ESCC. The possibility of using PRL-1 and PRL-3 as the therapeutical target is also discussed.

Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases.

PURPOSE: The PRL-3 mRNA is consistently elevated in metastatic samples derived from colorectal cancers. We sought to generate a specific PRL-3 monoclonal antibody (mAb) that might serve as a potential diagnostic marker for colorectal cancer metastasis. EXPERIMENTAL DESIGN: PRL-3 is one of three members (PRL-1, PRL-2, and PRL-3) in a unique protein-tyrosine phosphatase family. Because the three PRLs are 76% to 87% identical in their amino acid sequences, it poses a great challenge to obtain mAbs that are specific for respective phosphatase of regenerating liver (PRL) but not for the other two in the family. We screened over 1,400 hybridoma clones to generate mAbs specific to each PRL member. RESULTS: We obtained two hybridoma clones specifically against PRL-3 and another two clones specifically against PRL-1. These antibodies had been evaluated by several critical tests to show their own specificities and applications. Most importantly, the PRL-3 mAbs were assessed on 282 human colorectal tissue samples (121 normal, 17 adenomas, and 144 adenocarcinomas). PRL-3 protein was detected in 11% of adenocarcinoma samples. The PRL-3- and PRL-1-specific mAbs were further examined on 204 human multiple cancer tissues. The differential expressions of PRL-3 and PRL-1 confirmed the mAbs' specificity. CONCLUSIONS: Using several approaches, we show that PRL-3- or PRL-1-specific mAbs react only to their respective antigen. The expression of PRL-3 in >10% of primary colorectal cancer samples indicates that PRL-3 may prime the metastatic process. These mAbs will be useful as markers in clinical diagnosis for assessing tumor aggressiveness.

[Expressions of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase in breast cancer and their correlations with prognosis].

OBJECTIVE: To study the expression of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNA in breast cancer and its correlation with prognosis. METHODS: Expression levels of TP, TS and DPD mRNA in 86 micro-selected breast cancer tissues and 9 normal breast tissues were detected by real-time quantitative PCR. RESULTS: The median expression levels of TP, TS and DPD mRNA in tumor tissue and in normal tissues were 16.54, 0.38, 2.47 and 11.75, 0.25, 8.33, respectively, there were no significant differences (P >0.05). The expression levels of TP, TS and DPD mRNA showed no association with tumor size, lymph node metastasis, pathological grade and clinical stage, except that of DPD showed a negative association with patients' ages. There was no significant difference in disease-free survival or overall survival between the patients with high and low TP or DPD mRNA levels. Disease-free survival tends to be better in the patients with low TS mRNA level than those with high TS mRNA, but the difference was not significant (P=0.069), while the overall survival showed a statistically difference (59.00 month and 70.30 month) (P=0.0496). CONCLUSION: The expression level of TS mRNA may serve as a prognostic marker for breast cancer patients.