Organization of personnel management in oil and gas corporation "Petrovietnam"

The petroleum industry is one of the most vital industries in the development strategy of Vietnam. Prevailing in this industry is Vietnam National Oil and Gas Group,“Petrovietnam”, operating under the directions of Ministry of Industry and Trade and controlling the oil and gas industry. A significant part in the steady growth path and the operational efficiency increment of the Group is contributed by the human resource policies. As oil prices were sharply declining, which began in 2014, a certain workforce reduction was planned by “Petrovietnam”, not only to deal with the situation but also to improve the quality of its workforce. Thus, managing human resources is one of the strategic tools of “Petrovietnam” corporate group

Detection of Cellular Senescence Reveals the Existence of Senescent Tumor Cells within Invasive Breast Carcinomas and Related Metastases

Oncogene-induced senescence is thought to constitute a barrier to carcinogenesis by arresting cells at risk of malignant transformation. However, numerous findings suggest that senescent cells may conversely promote tumor growth and metastatic progression, for example, through the senescence-associated secretory phenotype (SASP) they produce. Here, we investigated the degree to which senescent tumor cells exist within untreated human primary breast carcinomas and whether the presence of senescent cancer cells in primary tumors is recapitulated in their matched lymph node metastases. For the detection of senescence, we used SA-β-galactosidase (SA-β-gal) staining and other senescence markers such as Ki67, p21, p53, and p16. In patients with invasive luminal A and B breast carcinomas, we found broad similarities in the appearance of cancer cells between primary tumors and their corresponding metastases. Analysis of lymph nodes from patients with other breast cancer subtypes also revealed senescent tumor cells within metastatic lesions. Collectively, our findings show that senescent tumor cells exist within primary breast carcinomas and metastatic lesions. These results suggest a potential role for senescent breast tumor cells during metastatic progression and raise the question as to whether the targeting of senescent tumor cells with anti-senescent drugs might represent a novel avenue for improved treatment of breast and other cancers

Functional characterization of circulating tumor cells (CTCs) from metastatic ER+/HER2− breast cancer reveals dependence on HER2 and FOXM1 for endocrine therapy resistance and tumor cell survival: Implications for treatment of ER+/HER2− breast cancer

Mechanisms of acquired endocrine resistance and late recurrence in patients with ER+/HER2− breast cancer are complex and not fully understood. Here, we evaluated mechanisms of acquired resistance in circulating tumor cells (CTCs) from an ER+/HER2− breast cancer patient who initially responded but later progressed under endocrine treatment. We found a switch from ERα-dependent to HER2-dependent and ERα-independent expression of FOXM1, which may enable disseminated ER+/HER2− cells to re-initiate tumor cell growth and metastasis formation in the presence of endocrine treatment. Our results also suggest a role for HER2 in resistance, even in ER+ breast cancer cells that have neither HER2 amplification nor activating HER2 mutations. We found that NFkB signaling sustains HER2 and FOXM1 expression in CTCs in the presence of ERα inhibitors. Inhibition of NFkB signaling blocked expression of HER2 and FOXM1 in the CTCs, and induced apoptosis. Thus, targeting of NFkB and FOXM1 might be an efficient therapeutic approach to prevent late recurrence and to treat endocrine resistance. Collectively our data show that CTCs from patients with endocrine resistance allow mechanisms of acquired endocrine resistance to be delineated, and can be used to test potential drug regimens for combatting resistance

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells

Background Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection. Methods HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike-in experiments in the CellSearch system. Twenty-one blood samples from 13 metastatic UC patients were analyzed for HER2-positive CTCs with CellSearch. Results HER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10-fold lower than in the HER-2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike-in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2. Conclusions Detection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial

\u27Normalizing\u27 the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin

Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-αvβ3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids’ reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAM$^{high}$CD49f$^{low}$CD24$^{+}$ and Int-αvβ3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-αvβ3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-αvβ3 were injected into a humanized mouse model, differentiated tumors developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-αvβ3 can potentially promote ‘normalization’ of their malignant phenotype and may prevent the malignant cells from progressing

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

A novel MEK-ERK-AMPK signalling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells

14 p.-9 fig.Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes (LNs) where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signalling mechanisms. We have analysed the involvement of the AMP-dependent kinase (AMPK) in the control of CCR7-dependent survival. A pro-apoptotic role for AMPK is suggested by the finding that pharmacological activators induce apoptosis, whereas knocking-down of AMPK with siRNA extends mDCs survival. Pharmacological activation of AMPK also induces apoptosis of mDCs in the LNs. Stimulation of CCR7 leads to inhibition of AMPK, through phosphorylation of Ser485, which was mediated by Gi/Gbut not by Akt or S6K, two kinases that control the phosphorylation of AMPK on Ser485 in other settings. Using selective pharmacological inhibitors, we show that CCR7-induced phosphorylation of AMPK on Ser485 is mediated by MEK and ERK. Coimmunoprecipitation analysis and Proximity Ligation Assays (PLA) indicate that AMPK associates with ERK, but not with MEK. The results suggest that in addition to Akt-dependent signalling mechanisms, CCR7 can also promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signalling axis. The data also suggest that AMPK may be a potential target to modulate mDC lifespan and the immune response.*This work was supported by grants awarded by Ministerio de Educación y Ciencia (SAF2005- 00801), Ministerio de Ciencia e Innovación (SAF2008-01468), Ministerio de Economía y Competitividad (SAF2011-23890), Ministerio de Economía y Competitividad (SAF2011-23890), RIER (RETICS Program/ Instituto de Salud Carlos III) (RD08/0075) and Consejería de Educación y Empleo from Comunidad de Madrid (Raphyme, S2010/BMD-2350). PLC was supported by a FPI scholarship (Ministerio de Economía y competitividad), CGM was supported by a contract associated to grant Raphyme S2010/BMD-2350 (Consejería de Educación y Empleo. Comunidad de Madrid). LGC and JFB were supported by scholarship FPU and I3P intro, respectively (Ministerio de Educación y Ciencia). JTB and CED were recipients of JAEdoc and I3P contracts (Consejo Superior de Investigaciones Científicas-Fondo Social Europeo). CDM was partially supported fellowship FPI, conferred by the Ministerio de Educación y Ciencia (Spain) and by a contract associated to grant RD08/0075 (RIER).Peer reviewe

Improved detection of sentinel lymph node metastases allows reliable intraoperative identification of patients with extended axillary lymph node involvement in early breast cancer

Background!#!An improved procedure that allows accurate detection of negative sentinel lymph node (SLN) and of SLN macrometastases during surgery would be highly desirable in order to protect patients from further surgery and to avoid unnecessary costs. We evaluated the accuracy of an intraoperative procedure that combines touch imprint cytology (TIC) and subsequent frozen section (FS) analysis. 2276 SLNs from 1072 patients with clinical node-negative early breast cancer were evaluated during surgery using TIC. Only cytologically-positive SLN were subsequently analysed with a single FS, preserving cytologically-negative SLN for the final postoperative histological diagnosis. Sensitivity, specificity and the accuracy of this approach were analysed by comparing the results from intra- and postoperative SLN and axillary node evaluation. This intraoperative method displayed 100% specificity for SLN metastases and was significantly more sensitive for prognostically relevant macrometastases (85%) than for micrometastases (10%). Sensitivity was highest for patients with two or more positive LNs (96%) than for those with only one (72%). 98% of the patients with final pN2a-pN3a were already identified during surgery. Patients who received primary axillary lymph node dissection had significantly more frequent metastases in further LNs (44.6%). Sensitivity was highest for patients with luminal-B, HER2+ and triple negative breast cancer and for any subtype if Ki-67 > 40%. TIC and subsequent FS of cytologically-positive SLNs is highly reliable for detection of SLN macrometastases, and allows accurate identification of patients with a high risk of extended axillary involvement during surgery, as well as accurate histological diagnosis of negative SLN