The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

Two-Dimensional Analysis Method for Highly Sensitive Detection of Dual MicroRNAs in Breast Cancer Cells.

Multiple biomarker detection is crucial for early clinical diagnosis, and it is significant to achieve the simultaneous detection of multiple biomarkers with the same nanomaterial. In this work, the hairpin DNA strands were selectively modified on the surface of gold nanorods (AuNRs) to construct two kinds of nanoprobes by rational design. When in the presence of dual microRNAs, AuNRs were assembled to form end-to-end (ETE) and side-by-side (SBS) dimers. Compared with a single AuNR, the dark-field scattering intensity and red color percentage variation of dimers were extremely distinguished, which could be developed for dual microRNA detection by combining the red color percentage and scattering intensity with the data processing method of principal component analysis to construct a two-dimensional analysis method. Especially, the fraction of AuNR dimers presented a linear relationship with the amount of microRNAs. Based on this, microRNA-21 and microRNA Let-7a in breast cancer cells were detected with the detection limits of 1.72 and 0.53 fM, respectively. This method not only achieved the sensitive detection of dual microRNAs in human serum but also realized the high-resolution intracellular imaging, which developed a new way for the oriented assembly of nanomaterials and biological detection in living cells.

Correlation of Serum Chemokine Ligand 14 with Barcelona Clinic Liver Cancer Stage, Lymphocyte Profile, and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma.

PURPOSE: To investigate the clinical relevance of serum chemokine ligand 14 (sCCL14) in patients with hepatocellular carcinoma (HCC) and the effect of transarterial chemoembolization (TACE) on the expression level of sCCL14 and the immune microenvironment. MATERIALS AND METHODS: In this prospective single-center observational study, 52 patients with HCC were recruited from January 2019 to December 2021, their clinical data and blood samples were collected, and the relationship between sCCL14 and progression-free survival (PFS) and TACE treatment response was analyzed. RESULTS: Among the 52 patients with HCC (Barcelona Clinic Liver Cancer [BCLC] Stage A, 25.0%; BCLC Stage B, 44.2%; and BCLC Stage C, 30.8%), patients with BCLC Stage C HCC had significantly lower sCCL14 levels than those of patients with BCLC Stages A and B HCC (P = .001). sCCL14 levels were significantly higher in the first week after treatment than before TACE treatment (P = .024). Baseline sCCL14 levels in patients who showed complete response after TACE treatment were significantly higher than those in other groups, and lower baseline sCCL14 values were associated with shorter PFS times. Multivariate Cox regression analysis showed that sCCL14 level (hazard ratio, 1.855; 95% CI, 1.039-3.311; P = .037) was an independent prognostic factor of PFS. sCCL14 levels negatively correlated with the proportion of B lymphocytes and regulatory T cells in circulating blood and positively correlated with the absolute T-lymphocyte count. CONCLUSIONS: sCCL14 may be a predictive biomarker of TACE effectiveness. Further studies are needed to validate and outline the role of combination immunotherapy.

Acquired tamoxifen resistance is surmounted by GW8510 through ribonucleotide reductase M2 downregulation-mediated autophagy induction.

Tamoxifen resistance is a major roadblock in the treatment of patients with breast cancer. Ribonucleotide reductase M2 (RRM2) was found to be involved in acquired resistance of breast cancer cells (BCCs) to tamoxifen. Here, we used GW8510, which has been identified as a potential RRM2 inhibitor, to evaluate the effect of RRM2 inhibition on reversing resistance of BCCs to tamoxifen and investigate its mechanisms. We showed that RRM2 overexpression played a key role in the development of acquired tamoxifen resistance in BCCs through downregulation of autophagy level. Combination treatment with tamoxifen and GW8510 significantly inhibited survival of the tamoxifen-resistant BCCs through induction of autophagic cell death compared to either of the two drugs. Furthermore, combination of tamoxifen and GW8510 resulted in marked growth inhibition of tamoxifen-resistant BBC xenograft tumor in vivo compared to tamoxifen or GW8510 alone. In conclusion, tamoxifen in combination with GW8510 can overcome acquired tamoxifen resistance in BCCs and may be a rational therapeutic approach against breast cancer with high RRM2 expression.

The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation.

OBJECTIVE: The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation (STC) was studied. MATERIALS AND METHODS: STC patients (n = 162) were randomly divided into experimental group (n = 84, orally taken GI-pill gastrointestinal electronic capsule and X-ray granule capsule) and control group (n = 78, orally taken X-ray granule capsule). Comparison of the time in colonic transit test between the two groups was conducted. The data of GI-pill gastrointestinal electronic capsule in vivo time, time of capsule passing through the colon, the number of high amplitude propagating contractions (HAPCs), and physiological response ratio were analyzed. RESULTS: There were no significant differences in the whole colonic transit test time, right colonic transit time, left colonic transit time, and rectosigmoid colonic transit time between experimental group and control group (p > 0.05). All patients had no abdominal pain, nausea, vomiting, black stool, difficulty in electronic capsule excretion, or any other discomfort during the test. CONCLUSION: GI-pill gastrointestinal electronic capsule can continuously evaluate the dynamic characteristics of digestive tract in STC patients and is consistent with X-ray granule capsule, which is meaningful to clinical application.

MicroRNA-326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR-326 in PD through the JNK signaling pathway by targeting X-box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR-326 and XBP1 was confirmed. The expression of miR-326 and XBP1 was measured in PD mice, and gain- and loss-function assay was conducted to examine the regulatory effect of miR-326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR-326 mimic and siRNA-XBP1 showed increased traction test scores, activation of autophagy, expression of LC3-II, c-Jun, and p-α-Syn, but diminished climbing time and expressions of iNOS, α-Syn, and p-c-Jun. The siRNA-XBP1 treatment could reverse the effect of miR-326 inhibitor on PD mice. Overexpression of miR-326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.

Squeezing transfer of light in a two-mode optomechanical system.

The squeezing transfer from a squeezed vacuum injected in one cavity to the output spectrum of the other cavity in an optomechanical system is investigated. By calculating the noise spectrum of the output field, it is found that two squeezing dips appear symmetrically located about the resonant point. Besides the contribution from the destructive interference between the noise fluctuation of the input field and its optomechanically modified one, the major part of the squeezing is transferred from the squeezed vacuum injected in the cavity. Additionally, it is shown that the adverse effects of the environment temperature on the output spectrum can be strongly suppressed by the injected squeezed field. This study can be useful in quantum communications via the optomechanical interface.

[Psychometric Evaluation of the Union Physio-Psycho-Social Assessment Questionnaire].

Objective To validate the Union Physio-Psycho-Social Assessment Questionnaire(UPPSAQ-70)and test its validity and reliability.Methods From April,2013 to July,2018,patients were asked to finish the computer evaluation of UPPSAQ-70 and Symptom Checklist 90(SCL-90)in Peking Union Medical College Hospital(PUMCH).Confirmatory factor analysis(CFA)was conducted on the SPSS 17.0,and the number of fixed factors was 8 factors and 3 factors.Amos 23.0 was used to verify the original 8-factor model,8-factor revision model,3-factor model,3-factor revision model,and single-factor model.Each factor of SCL-90 was used as the calibration standard to calculate the correlation coefficient between factors.The retest reliability was tested by the outpatients in PUMCH in July,2018.Results Exploratory factor analysis indicated that the 8-factor revised model included:depression,anxiety and fatigue,sleep,physical discomfort,sexual function,happiness and satisfaction,hypochondria,and social anxiety.The 3 factors revised model included that:psychological,physiological and social dimension.Confirmatory factor analysis indicated that the 8-factor modified model was superior to the 3-factor model and the single-factor model: χ 2=10 410.4,df=1862,RMSEA=0.07,CFI=0.753,and NFI=0.715.With SCL-90 as the standard criteria,except the low correlation coefficient between emotional scale and depression(r=0.600)and anxiety(r=0.520),the correlation coefficients of other symptoms were below 0.5.The chronbach's α between each factor and total score of UPPSAQ-70 was between 0.823 and 0.904,and the Chronbach's α coefficient of the whole scale was between 0.954 and 0.956 after each item was deleted.The retest reliability of the scale of 32 participants Chronbach's α was 0.847.Each item of the scale measured between one week was significantly correlated(P<0.05). Conclusion UPPSAQ-70 is a good scale for evaluating overall health status and is especially feasible in general hospitals.

MicroRNA-184 inhibits proliferation and promotes apoptosis of human colon cancer SW480 and HCT116 cells by downregulating C-MYC and BCL-2.

This study aimed to investigate the effects of microRNA-184 (miR-184) on the proliferation and apoptosis of human colon cancer cells through the regulation of C-MYC and BCL-2. Human colon cancer tissues were selected as case group, and adjacent normal tissues were as control group. Human colon cancer SW480 and HCT116 cells were allocated into blank, miR-184 mimic negative control (mimic-NC), miR-184 inhibitor NC (inhibitor-NC), miR-184 mimic, and miR-184 inhibitor groups. Flow cytometry, Annexin V/PI and MTT assay were used to examine the cell cycle, apoptosis and viability. The expressions of C-MYC, BCL-2 and miR-184 were detected via immunohistochemistry, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR). C-MYC and BCL-2 were direct targets to miR-184. The growth of colon cancer cells in the miR-184 mimic group was inhibited and exhibited an increase in apoptosis. Cell growth in the miR-184 mimic group was increased in addition to the inhibition of apoptosis. Compared with miR-184 mimic group, the expressions of C-MYC and BCL-2 in miR-184 inhibitor group were increased. The expressions of C-MYC and BCL-2 in colon cancer tissues exhibited high levels of expression, while miR-184 displayed relatively low levels in comparison to the adjacent normal tissues. An association was detected regarding the expressions of miR-184, C-MYC and BCL-2 with the differentiation, invasion depth and lymph node metastasis. MiR-184 expression was negatively related to C-MYC and BCL-2 expressions. Our study suggested that miR-184 could inhibit proliferation and promote apoptosis of colon cancer cells by down-regulating expressions of C-MYC and BCL-2.

Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR stimulated by TGF-ß1 secretion.

BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the transactivation of target LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA-MB-231 was conducted to confirm the mechanism in vivo. RESULTS: Here we reported that TGF-ß1 was top one highest level of cytokine secreted by CAFs as revealed by cytokine antibody array. Paracrine TGF-ß1 was essential for CAFs induced EMT and metastasis in breast cancer cells, which is a crucial mediator of the interaction between stromal and cancer cells. CAF-CM significantly enhanced the HOTAIR expression to promote EMT, whereas treatment with small-molecule inhibitors of TGF-ß1 attenuated the activation of HOTAIR. Most importantly, SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides -386 and -398, -440 and -452, suggesting that HOTAIR was a directly transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs-induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model. CONCLUSIONS: Our findings demonstrated that CAFs promoted the metastatic activity of breast cancer cells by activating the transcription of HOTAIR via TGF-ß1 secretion, supporting the pursuit of the TGF-ß1/HOTAIR axis as a target in breast cancer treatment.

Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction.

Although chemotherapeutic regimen containing gemcitabine is the first-line therapy for advanced lung squamous cell carcinoma (LSCC), gemcitabine resistance remains an important clinical problem. Some studies suggest that overexpressions of ribonucleotide reductase (RNR) subunit M2 (RRM2) may be involved in gemcitabine resistance. We used a novel RRM2 inhibitor, GW8510, as a gemcitabine sensitization agent to investigate the therapeutic utility in reversing gemcitabine resistance in LSCC. Results showed that the expressions of RRM2 were increased in gemcitabine intrinsic resistant LSCC cells upon gemcitabine treatment. GW8510 not only suppressed LSCC cell survival, but also sensitized gemcitabine-resistant cells to gemcitabine through autophagy induction mediated by RRM2 down-regulation along with decrease in dNTP levels. The combination of GW8510 and gemcitabine produced a synergistic effect on killing LSCC cells. The synergism of the two agents was impeded by addition of autophagy inhibitors chloroquine (CQ) or bafilomycin A1 (Baf A1), or knockdown of the autophagy gene, Bcl-2-interacting protein 1 (BECN1). Moreover, GW8510-caused LSCC cell sensitization to gemcitabine through autophagy induction was parallel with impairment of DNA double-strand break (DSB) repair and marked increase in cell apoptosis, revealing a cross-talk between autophagy and DNA damage repair, and an interplay between autophagy and apoptosis. Finally, gemcitabine sensitization mediated by autophagy induction through GW8510-caused RRM2 down-regulation was demonstrated in vivo in gemcitabine-resistant LSCC tumor xenograft, further indicating that the sensitization is dependent on autophagy activation. In conclusion, GW8510 can reverse gemcitabine resistance in LSCC cells through RRM2 downregulation-mediated autophagy induction, and GW850 may be a promising therapeutic agent against LSCC as it combined with gemcitabine.

Complete genome sequence of a Capsicum chlorosis virus in China and the structural variation and evolutionary origin of its S RNA intergenic region.

The complete genome sequence of a Capsicum chlorosis virus from China (CaCV-Hainan) was determined. The tripartite genome of CaCV-Hainan consists of small (S), medium (M), and large (L) RNAs of 3629, 4859, and 8912 nucleotides (nt), respectively. The S and M RNAs contain intergenic regions (IGRs) of 1348 and 462 nt, respectively. Strikingly, sequence comparisons among CaCV isolates revealed that the S RNA IGR of CaCV-Hainan derived from the CaCV-Qld-3432 Australia isolate through deletion of two stretches of 25- and 325-nt sequences within the S RNA IGR of CaCV-Qld-3432. Moreover, the S RNA IGR of CaCV-Hainan was inserted with two stretches of 10- and 20-nt sequences of an unknown origin. The S RNA IGR of CaCV-Ph from Taiwan and CaCV-NRA from Thailand also derived from the CaCV-Qld-3432 through deletion of 218-nt sequences. Our findings provide valuable new insight into the structural variations and evolutionary origin of CaCV IGRs.

Transplantation of EPCs overexpressing PDGFR-ß promotes vascular repair in the early phase after vascular injury.

BACKGROUND: Endothelial progenitor cells (EPCs) play important roles in the regeneration of the vascular endothelial cells (ECs). Platelet-derived growth factor receptor (PDGFR)-ß is known to contribute to proliferation, migration, and angiogenesis of EPCs, this study aims to investigate effects of transplantation of EPCs overexpressing PDGFR-ß on vascular regeneration. METHODS: We transplanted genetically modified EPCs overexpressing PDGFR-ß into a mouse model with carotid artery injury. After 3 days of EPCs transplantation, the enhanced green fluorescent protein (EGFP)-expressing cells were found at the injury site and the lining of the lumen by laser scanning confocal microscope (LSCM). At 4, 7, and 14 days of the carotid artery injury, reendothelialization was evaluated by Evans Blue staining. Neointima formation was evaluated at day 14 with hematoxylin and eosin (HE) staining by calculating the neointimal area, medial area, and neointimal/media (NI/M) ratio. Intimal cell apoptosis was evaluated using TUNEL assay. Then we tested whether PDGF-BB-induced VSMC migration and PDGF-BB's function in reducing VSMC apoptosis can be attenuated by EPCs overexpressing PDGFR-ß in a transwell co-culture system. RESULTS: Our results showed that EPCs overexpressing PDGFR-ß accelerates reendothelialization and mitigates neointimal formation at 14 days after injury. Moreover, we found that there is great possibility that EPCs overexpressing PDGFR-ß enhanc VSMC apoptosis and suppress VSMC migration by competitive consumption of PDGF-BB in the early phase after carotid artery injury in mice. CONCLUSIONS: We report the first in vivo and in vitro evidence that transplantation of genetically modified EPC can have a combined effect of both amplifying the reendothelialization capacity of EPCs and inhibiting neointima formation so as to facilitate better inhibition of adverse remodeling after vascular injury.

Retrospective Analysis of Liaison Psychiatric Service in Elderly Inpatients in A General Hospital.

Objective To analyze liaison psychiatric service in a geriatric ward in a big general hospital and explore the way to improve accessibility of geriatric psychiatric service in general hospitals. Methods Elderly inpatients aged 65 years old or more admitted to a geriatrics ward in Peking Union Medical College Hospital in 7 years duration (January 2008 to December 2014) were enrolled in the study. Liaison psychiatrists attended ground round combined with psychiatric consultation from January 2008 to December 2009 (T1 period). Comprehensive geriatric assessment,geriatric interdisciplinary team services and psychiatric consultation were conducted from January 2010 to December 2014 (T2 period). Consultation rate,reasons for referral,psychiatric diagnoses,length of stay,and medical expense were compared between different periods.Results Among 1230 geriatric inpatients,383 patients were enrolled in liaison psychiatric service,and 511 individual consultations happened.The consultation rate for T1 and T2 were 19.7% and 33.8%,respectively (P=0.000).The dominating reasons for referral were current emotional symptoms (30.4%) and current psychiatric symptoms (28.3%) in T1 and current emotional symptoms (65.3%) and medically unexplained symptoms (12.8%) in T2 (P=0.000). For length of stay,consultation group lasted for (199.2±40.0) days,and non-consultation group lasted for (71.3±16.6) days(P=0.004) in T1;(22.0±2.4) days and (22.6±1.6) days(P=0.834) in different groups in T2 respectively. The medical expense were (243 000±44 000) RMB for consultation group and (79 000±18 000) RMB for non-consultation group(P=0.040) in T1 and (18 000±2 000) RMB and (21 000±1 000) RMB (P=0.302) in different groups in T2 respectively. The prevalence rate for psychiatric disorders revealed by liaison psychiatrists was 15.8% in T1 and 29.8%in T2 (P=0.000) in the geriatric ward. Conclusions Elderly inpatients are vulnerable population for psychiatric disorders. Therefore,psychiatrist should be an important member in geriatric interdisciplinary team. Combination of comprehensive geriatric assessment,psychiatric consultation and geriatric interdisciplinary team is very efficient model in general hospital settings to improve the accessibility of psychiatric services in elderly in China.

Hemodynamic characteristics of high-altitude headache following acute high altitude exposure at 3700 m in young Chinese men.

BACKGROUND: This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure. METHODS: The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined at two altitudes (500 and 3700 m). RESULTS: HAH was characterized by increased HR and cardiac output (CO) and lower saturation pulse oxygen (SpO(2)) (all p < 0.05). The change in tricuspid regurgitation was also different between the HAH positive (HAH+) and HAH negative (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (V(m)), systolic (V(s)) and diastolic (V(d)) velocities in the basilar artery (BA; all p < 0.05) and a faster V(d) ( 25.96 ± 4.97 cm/s vs. 24.76 ± 4.76 cm/s, p = 0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also significantly different between the two groups. The pulsatility index (PI) and resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or right MCA in different regressions) were independent predictors for HAH, whereas CO/HR and ΔV(d) (V(d) difference between bilateral VAs) were independent risk factors for HAH at 3700 m. CONCLUSIONS: HAH was characterized, in part, by increased systemic hemodynamics and posterior cerebral circulation, which was reflected by the BA and left VA velocities, and lower arterial resistance and compliance. Furthermore, baseline CO and V(m) in left VA or right MCA at sea level were independent predictors for HAH, whilst bilateral VA asymmetry may contribute to the development of HAH at high altitude.

(6-Chloropyridazin-3-yl)ferrocene.

The asymmetric unit of the title compound, [Fe(C5H5)(C9H6ClN2)], contains two independent mol-ecules in which the cyclo-penta-dienyl rings are almost parallel, making dihedral angles of 2.16 (4) and 2.71 (5), and the dihedral angles between the pyridazinyl and substituted cyclo-penta-dienyl rings are 9.65 (5) and 11.53 (8)°. In the crystal, mol-ecules are linked by C-H⋯N hydrogen bonds into chains along the c-axis direction.

Flotillin-2 is associated with breast cancer progression and poor survival outcomes.

BACKGROUND: Flotillin-2 (FLOT2) has been implicated in several signaling pathways in tumor cells. Our study aimed to investigate the expression pattern and clinicopathological significance of FLOT2 in patients with breast cancer. METHODS: The expression level of FLOT2 in normal breast epithelial cells, breast cancer cell lines, and four breast cancer biopsies paired with adjacent noncancerous tissues were quantified using real-time RT-PCR and Western blotting. FLOT2 protein expression was analyzed in 171 archived paraffin-embedded breast cancer samples using immunohistochemistry (IHC). Statistical analyses were performed to evaluate the clinicopathological significance of FLOT2 expression. RESULTS: FLOT2 was significantly upregulated in breast cancer cell lines and tissue samples compared with normal cells and adjacent noncancerous breast tissues, respectively. IHC analysis revealed high expression levels of FLOT2 in 82 of 171 (48.0%) breast cancer specimens. Statistical analysis revealed that FLOT2 expression was significantly correlated with clinical stage (P < 0.001), T classification (P < 0.001), M classification (P < 0.001), histological differentiation (P = 0.005) and ErbB2 expression (P = 0.003). Patients with higher levels of FLOT2 expression had a shorter overall survival duration than patients with lower FLOT2 expression levels. Multivariate analysis suggested that FLOT2 expression was an independent prognostic marker for survival in patients with breast cancer. CONCLUSIONS: The current results demonstrated that high FLOT2 protein expression was associated with poor outcomes in patients with breast cancer. FLOT2 could be used as a prognostic biomarker for breast cancer progression.