Elevated miR-21 is associated with poor prognosis in non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Increasing studies have investigated the prognostic value of high miR-21 expression in non-small cell lung cancer (NSCLC) with inconsistent results. We conducted this meta-analysis to explore whether the expression of miR-21 was associated with prognosis in NSCLC patients. MATERIALS AND METHODS: We systematically searched Medline, EMBASE, Web of Science and Cochrane Library for relevant studies. Studies exploring the relationship between miR-21 expression and NSCLC prognosis and clinical pathology, and reporting enough data to get the hazard ratio (HR) and 95% confidence intervals (CIs), were included. Random- or fixed-effect models were employed to calculated pooled hazard ratios (HRs) or risk ratio and 95% confidence intervals (95% CIs). RESULTS: A total of 28 eligible studies, including 24 for prognosis, 16 for clinicopathological features were identified. Our results revealed that elevated miR-21 was related to unfavorable overall survival (OS) in NSCLC (HR = 1.960, 95% CI = 1.510-2.554, p = 0.000). Similar results were found in disease-free survival, relapse-free survival, and cancer-special death. In a meta-analysis of clinical pathology, overexpressed miR-21 was significantly related to lung adenocarcinoma, larger tumor size, and advanced clinical stage. CONCLUSIONS: Our meta-analysis suggested that miR-21 may function as an unfavorable biomarker of prognosis in NSCLC patients.

REPAIR EFFECTS OF UMBILICAL CORD MESENCHYMAL STEM CELLS ON PODOCYTE DAMAGE OF IgA NEPHROPATHY.

This study aimed to explore the influence of umbilical cord mesenchymal stem cells (UMSC) on stem cell homing and glomerular mesangial cell (GMC) after intravenous injection performed on mice tails with IgA nephropathy (IgAN) and its possible mechanism, which provide a new way and theoretical basis for the application of stem cell transplantation (SCT) in kidney disease treatment. Specific pathogen free (SPF) male Kunming mice were randomly divided into groups. A complex method applying bovine serum albumin (BSA) gavage, hypodermic injection of CCl4 and lipopolysaccharide (LPS) was used for building IgAN mice model. In addition, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and cluster of differentiation (CD) 44 were observed by Masson staining and detected with immunohistochemistry (IHC) to confirm homing and location of mesenchymal stem cells (MSCs). Moreover, Western Blot was used for detecting VEGF and CTGF so as to explore the possible mechanism of applying UMSC in treating IgAN. Masson staining indicated that fibrosis degree of MSCs in treatment group was significantly lower than in negative control group after stem cell treatment. Routine urine test explained that proteinuria in treatment group were (7.15±0.31), (4.87±0.22), (2.95±0.16) g/24 h and (12.00±1.38) g/24 h in model group (P less than 0.05). MSCs were observed to be located in glomerulus and renal interstitium by IHC detection of CD44 and IHC qualitative observation of VEGF and CTGF had different positive expressions in three groups. Furthermore, different expressions of VEGF and CTGF were observed quantitatively by Western Blot. Fibrosis degree of renal tissue relieves, hematuresis and proteinuria eases and IgAN symptoms obviously improve after UMSC treatment, which hints that the treatment of HUMSC has protective effect on IgAN mice model.

Ovarian endometriosis associated with carcinoma and sarcoma: case report.

Endometriosis is a common clinical disorder that shares certain characteristics, metastasis and recurrence, with malignant neoplasms. Most malignant ovarian tumors arising from endometriosis are clear cell carcinoma or endometrioid adenocarcinoma. Few reports exist of sarcoma associated with endometriosis, and even fewer exist of multiple types of malignancies occurring simultaneously. Here, we report the case of a 32-year-old woman who presented with infertility and a pelvic mass. She underwent exploratory laparotomy and bilateral salpingo-oophorectomy. She was then referred to our institution for treatment recommendation. The pathologic findings revealed bilateral endometrioid adenofibroma of low malignant potential, which was associated with endometrioid intraepithelial carcinoma in the left ovary and high-grade sarcoma in the right ovary. Both tumors seemed to have arisen from endometriosis. She was treated with 75 mg/m2 of doxorubicin and 10 g/m2 of ifosfamide every three weeks for eight courses. She was later found to have bilateral brain metastases, which were resected and treated by whole-brain irradiation. She was again treated with doxorubicin and ifosfamide. The optimal treatment for endometriosis-associated ovarian cancer depends on the type of malignancy; simultaneously occurring multiple tumor types should be treated individually.

Erosive osteoarthritis during treatment with bevacizumab and paclitaxel in a patient with recurrent papillary serous carcinoma of the ovary.

Bevacizumab (BVC) is currently used in recurrent ovarian cancer and as part of the initial treatment for ovarian cancer. The most serious toxicities associated with BVC include gastrointestinal perforations, delayed wound healing, and hemorrhage. Arthritis had never been addressed in patients who received BVC treatment. This is the first case report of arthritis emergence linked to BVC administration. A 59-year-old female with recurrent ovarian cancer received multiple hormonal and cytotoxic regimens for 5 years and then developed erosive osteoarthritis of the hands secondary to BVC and paclitaxel. This effect was confirmed by a significant improvement in her symptoms and signs, after treatment was discontinued.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction.

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m(2), in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60-89, 30-59, and <30 mL/min/1.73 m(2), respectively). Twenty-nine patients were included in the study--22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1-52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

Cloning of new members of heat shock protein HSP101 gene family in wheat (Triticum aestivum (L.) Moench) inducible by heat, dehydration, and ABA(1).

We have cloned two cDNAs, TaHSP101B and TaHSP101C, encoding two heat stress-inducible members of HSP101/ClpB family in bread wheat (Triticum aestivum (L.) Moench.). Proteins encoded by these cDNAs are highly similar at the primary sequence level and diverged from the previously reported TaHSP101 (designated TaHSP101A) both in the consensus ATP/GTP-binding region II and in the carboxy terminal region. The HSP101 gene was determined to be a single copy gene or a member of a small gene family in hexaploid wheat. Messages encoding HSP101 proteins were inducible by heat stress treatments in both wheat leaves and roots. Accumulation of the TaHSP101C mRNA was less abundant than that of TaHSP101B mRNA. We are showing for the first time that in addition to heat stress, expression of HSP101 mRNAs in wheat leaves was induced by a 2-h dehydration and a treatment with 5x10(-5)M ABA, but not affected by chilling or wounding, indicating that HSP101 proteins may be involved in both heat and drought responses in wheat.

[AFLP analysis of photoperiod-sensitive genic male sterile(PGMS) rice mutant lines].

The reaction conditions for rice AFLP assay were optimized. The relative efficiencies for polymorphism detection of RFLP, RAPD and AFLP were compared through the analysis between a pair of PGMS allelic mutant lines(NK58S and NK58F). Results indicated that the efficiency for polymorphism detection in rice is in the order of AFLP > RAPD > RFLP, and also indicated that AFLP is a powerful DNA molecular marker technique for polymorphism detection, especially in the cases of extremely low polymorphism, such as isogeneic lines and allelic mutant lines. The advantages and disadvantages of these three molecular marker systems were discussed. Using AFLP in conjunction with bulked segregating analysis, 5106 AFLP loci were screened and 9 of them showed polymorphism between NK58S and NK58F, 4 of the polymorphic AFLP products were cloned, Southern bloting analysis showed that two of them were single copy sequences while the other two were low copy sequences in rice genome.

Quantitative trait loci for root-penetration ability and root thickness in rice: comparison of genetic backgrounds.

Drought is the major abiotic stress limiting rice (Oryza sativa) production and yield stability in rainfed lowland and upland ecosystems. Root systems play an important role in drought resistance. Incorporation of root selection criteria in drought resistance improvement is difficult due to lack of reliable and efficient screening techniques. Using a wax-petrolatum layer system simulated to compacted soil layers, root traits were evaluated in a doubled haploid (DH) population derived from the cross between 'IR64' and 'Azucena'. Twelve putative QTLs (quantitative trait loci) were detected by interval mapping comprising four QTLs for root-penetration ability, four QTLs for root thickness, two QTLs for penetrated root number, and two QTLs for total root number. These QTLs individually explained 8.4% to 16.4% of the phenotypic variation. No QTL was detected for maximum penetrated root length by interval mapping. One QTL located between RG104 and RG348 was found to influence both root-penetration ability and root thickness. QTLs for root-penetration ability and root thickness were compared across two populations, 'IR64'-'Azucena' and 'CO39'-'Moroberekan', and different testing conditions. The identified consistent QTLs could be used for marker-assisted selection for deep and thick roots with high root-penetration ability in rice.

Tagging and mapping the thermo-sensitive genic male-sterile gene in rice (Oryza sativa L.) with molecular markers.

The thermo-sensititve genic male-sterile (TGMS) gene in rice can alter fertility in response to temperature and is useful in the two-line system of hybrid rice production. However, little is known about the TGMS gene at the molecular level. The objective of this study was to identify molecular markers tightly linked with the TGMS gene and to map the gene onto a specific rice chromosome. Bulked segregant analysis of an F2 population from 5460s (a TGMS mutant line) x 'Hong Wan 52' was used to identify RAPD markers linked to the rice TGMS gene. Four hundred RAPD primers were screened for polymorphisms between the parents and between two bulks representing fertile and sterile plants; of these, 4 primers produced polymorphic products. Most of the polymorphic fragments contained repetitive sequences. Only one singlecopy sequence fragment was found, a 1.2-kb fragment amplified by primer OPB-19 and subsequently named TGMS1.2. TGMS1.2 was mapped on chromosome 8 with a RIL population and confirmed by remapping with a DHL population. Segregation analysis using TGMS1.2 as a probe indicated that TGMS1.2 both consegregated and was lined with the TGMS gene in this population. It is located about 6.7 cM from the TGMS gene. As TGMS1.2 is linked to the TGMS gene, the TGMS gene must be located on chromosome 8.

[The establishment of genomic DNA libraries for the human malaria parasite Plasmodium falciparum].

The DNA of Plasmodium falciparum has been purified and fragmented with restriction endonuclease BamHI. The fragments have been incorporated in vitro into derivatives of bacteriophage lambda EMBL4 digested with BamHI and Sal I. The recombinant mixture has been ligated and packaged in vitro. The recombinant phages have been identified in E. coli L95 host cell and the libraries have been established in which most of the parasite DNA is represented. The ligation proportion of vector to insert is 3:1. The recombinant phages of 4 x 10(5) have been obtained. By plaque hybridization, we have been able to recover from these libraries specific clones containing repetitive DNA sequences.

[Ultrastructural study of fallopian tubes after occlusive sterilization with phenol-mucilage].

PIP: Tubal biopsy specimens were obtained at the time of tubal reversal in 10 women who had had occlusive sterilization by phenol-mucilage; the interval between sterilization to reversal operation ranged from 1-7 years. Transmission electron microscopy revealed that at the site of the tubal occlusion there were abundant collagen fibrils, a few fibrocytes, and scattered lymphocytes. The mucosal epithelium adjacent to the tubal occlusion showed simple columnar ciliated cells and secretory cells. No pathological changes in these cells were seen. 5 of the 10 patients had become pregnant after 1 year following the reversal procedure. Author evidence suggests that the occlusive sterilization with phenol-mucilage does not induce any malignant changes in tubal tissues even after a long time. It is indicated that this method of sterilization is safe. However, bacteria were found in 1 mucosal epithelial specimen and attention should be paid to this observation. (author's modified)^ieng

Immunoregulatory activity of the T-cell receptor alpha chain demonstrated by retroviral gene transfer.

We have previously described an antigen-specific I-Ad-restricted T-cell hybridoma, A1.1, that constitutively releases an antigen-specific immunoregulatory activity into supernatants. Using retrovirally mediated gene transfer, we have found that transfer of the T-cell receptor alpha chain (TCR alpha) gene from A1.1 to a number of other T-cell hybridomas effectively transferred the ability to produce the activity. Gene transfer of the TCR beta chain (TCR beta), however, did not transfer this ability. The regulatory activity from cells expressing the A1.1 TCR alpha bound to and was eluted from an anti-TCR alpha monoclonal antibody and displayed fine antigenic specificity identical to that of supernatants from A1.1. The possibility that this activity represents a secreted form of the TCR alpha (as opposed to shed cell-surface TCR) was examined in BW1100 cells, lacking TCR alpha and TCR beta, which produced the antigen-specific activity after gene transfer of the A1.1 TCR alpha gene. The expression of the immunoregulatory activity in supernatants correlated with a direct antigen-binding activity as detected by ELISA, thus raising the possibility that antigen binding is relevant to the mechanism of action of the soluble TCR alpha. We discuss these observations and our earlier studies suggesting an immunoregulatory role for soluble TCR alpha.

A T helper cell hybridoma produces an antigen-specific regulatory activity. Relationship to the T cell receptor by serology and antigenic fine specificity.

We have previously shown that a T cell hybridoma, A1.1, constitutively produces an Ag-specific regulatory factor with specificity for poly-18, a synthetic polypeptide. This cell also responds to poly-18 plus I-Ad by producing lymphokines. The antigenic specificity of the factor and the T cell appeared to be the same. This suggested the possibility that some part of the TCR, responsible for antigenic specificity of the cell, also imparts specificity to the A1.1-derived factor. This was supported by the observation that the factor was bound and eluted from a monospecific anti-TCR antiserum. Further, we demonstrated that antisense oligodeoxynucleotides corresponding to the TCR V alpha of A1.1 (but not TCR V beta) block production of the Ag-specific factor. Herein, we report recent findings that strengthen the proposed relationship between the TCR and the A1.1-derived factor. The factor was bound and eluted from a monoclonal anti-TCR C alpha antibody, but not from anti-TCR beta, anti-V beta 6, nor anti-CD3 epsilon. The anti-TCR C alpha antibody bound a Mr 46-kDa protein from A1.1 supernatants, which is the same apparent size at which activity could be eluted from an SDS-PAGE gel separation of concentrated factor. Antigenic fine-specificity analysis revealed that two amino acids in poly-18 are critical for the recognition of the antigen by the Ag-specific factor. These two amino acids appear to be those recognized by the TCR. The factor that was bound and eluted from the monoclonal anti-TCR C alpha showed this fine-specificity as well. This, combined with our earlier studies, supports the view that the A1.1-derived factor is encoded, at least in part, by TCR-alpha.

A helper T cell clone produces an antigen-specific molecule (T-ABM) which functions in the induction of suppression.

Among Ly-1+,2-T cells there appears to be two independent modes of antigen recognition. Helper and cytotoxic Ly-1 T cells recognize antigen only in the context of I region products whereas regulatory T cells, such as T suppressor inducer cells, produce antigen-specific, antigen-binding molecules (T-ABM). These T-ABM often have been found to form a part of biologically active, antigen-specific regulatory factors. A number of environmental conditions effect whether a foreign antigen will produce a positive response leading to immunity or a negative one leading to tolerance. Many of the conditions which favor the induction of suppressor T cells simultaneously preclude the proper interaction of antigen presenting cells with helper T cells. This parallel led us to ask whether helper T cells perform at least two, apparently opposite functions: a) under conditions favoring immunity helper T cells produce lymphokines to activate immune effector cells, and b) under conditions favoring suppression they produce molecules which function in suppressor cell induction. Therefore, this question relates to the mechanisms by which an immune response is switched into either a positive (help) or negative (suppressive) track. In addition, it begins to address the relationship between the different modes of antigen recognition exhibited by helper T cells vs. T suppressor inducer cells (see above). To explore this problem we employed an antigen-specific, I-Ak restricted helper T cell clone as the purest available source of helper T cells. We presented antigen to the cloned T cells under conditions which favor suppression rather than help (for example, by ultraviolet irradiation of the antigen-presenting cells) and collected supernatants 48 hrs later. The supernatants were then examined for activity in a functional assay for antigen-specific suppressor factors. Our results indicate that under conditions favoring suppression, a T-ABM was produced which functioned in the antigen-specific induction of suppression in vitro. The T-ABM had the same antigen specificity as that exhibited by the helper T cell and was therefore probably derived from the clone. This observation introduces the possibility that the interaction between antigen-presenting cells and helper T cells is a crucial decision point in the immune response which can lead to either immunity or suppression. The latter would be achieved through the production, by helper T cells, of an antigen-specific component of T suppressor inducer factor (i.e., the T-ABM). The possible relationship between T-ABMs and the T cell receptor is discussed.