[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Targeting the HMGA2 oncogene by miR-498 inhibits non-small cell lung cancer biological behaviors.

OBJECTIVE: Previous study reported that miR-498 served as a tumor suppressor in non-small cell lung cancer (NSCLC), but the underlying mechanism remains largely unknown. The aim of this study is to investigate the role of miR-498 and its target gene HMGA2 in NSCLC progression. PATIENTS AND METHODS: The expression of miR-498 was assessed in clinical NSCLC specimens and cell lines using RT-PCR. Overexpression of miR-498 and transfection of pLenti-HMGA2 were performed in A549 cells. Cell proliferation, apoptosis, migration, and invasion were determined using cell counting kit-8 (CCK-8) assay, clone formation assay, flow cytometry, and transwell assay, respectively. Luciferase reporter assays were performed to analyze the regulation of putative target of miR-498. Western blot was used to detect the levels of HMGA2 in A549 cells. RESULTS: MiR-498 was found to be down-regulated in NSCLC tissues and cell lines. After miR-498 mimics transfection, cell proliferation, migration, and invasion were significantly suppressed in the NSCLC cells. Mechanistically, bioinformatic analysis predicted that miR-498 may target the 3'-UTR of HMGA2 and suppressed its translation, and was further confirmed by luciferase assay. Furthermore, restoration of HMGA2 expression completely rescued the inhibitory effect of miR-498 in NSCLC cells. CONCLUSIONS: This paper revealed that miR-498 may serve as a tumor suppressor in NSCLC through targeting HMGA2, suggesting that miR-498 could represent a novel target for effective therapies.

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo.

This study aimed to investigate the effect of RNAi-mediated silencing of the Livin gene on biological properties of the colon cancer cell line LoVo. Interference vectors pSilencer4.1-Ll and pSilencer4.1-L2 targeting the Livin gene were constructed and transfected into LoVo cells. The expression of the Livin gene was determined by RT-PCR and Western blotting. The apoptosis, cell cycle, colony formation, proliferation of LoVo cells, as well as their sensitivity to cisplatin, were detected by flow cytometry, colony formation assay and MTT. Livin mRNA and protein expression in LoVo cells could be effectively silenced by pSilencer4.1-Ll but not pSilencer4.1-L2. In the pSilencer4.1-Ll transfection group, the apoptosis rate of LoVo cells was significantly higher than in the control group (24.2 ± 3.2 vs 8.1 ± 1.4%, P < 0.01), and after 72 h, cell proliferation was clearly decreased (about 70% inhibition). Compared with the control group, the colony formation rate in pSilencer4.1-Ll transfection group was obviously decreased (15 ± 4.6 vs 85 ± 5.8%, P < 0.01), with increased proportion of S phase cells (45.7 ± 4.9 vs 28.0 ± 3.0%, P < 0.01), decreased proportion of G1 phase cells (43.0 ± 5.2 vs 62.8 ± 5.1%, P < 0.01), and increased sensitivity to cisplatin (apoptosis rate increased from 43.4 ± 6.9 to 65.3 ± 6.2%, P < 0.01). pSilencer4.1-Ll can effectively silence Livin gene expression in LoVo colon cancer cells, inhibit cell proliferation and colony formation, induce apoptosis, and enhance sensitivity to cisplatin.

Amorphous nickel hydroxide nanospheres with ultrahigh capacitance and energy density as electrochemical pseudocapacitor materials.

Among numerous active electrode materials, nickel hydroxide is a promising electrode in electrochemical capacitors. Nickel hydroxide research has thus far focused on the crystalline rather than the amorphous phase, despite the impressive electrochemical properties of the latter, which includes an improved electrochemical efficiency due to disorder. Here we demonstrate high-performance electrochemical supercapacitors prepared from amorphous nickel hydroxide nanospheres synthesized via simple, green electrochemistry. The amorphous nickel hydroxide electrode exhibits high capacitance (2,188 F g(-1)), and the asymmetric pseudocapacitors of the amorphous nickel hydroxide exhibit high capacitance (153 F g(-1)), high energy density (35.7 W h kg(-1) at a power density of 490 W kg(-1)) and super-long cycle life (97% and 81% charge retentions after 5,000 and 10,000 cycles, respectively). The integrated electrochemical performance of the amorphous nickel hydroxide is commensurate with crystalline materials in supercapacitors. These findings promote the application of amorphous nanostructures as advanced electrochemical pseudocapacitor materials.

Molecular analysis and frequency of Staphylococcus aureus virulence genes isolated from bloodstream infections in a teaching hospital in Tianjin, China.

Staphylococcus aureus is an important cause of bloodstream infections worldwide. We examined the prevalence of genes that encode erythromycin ribosome methylase and bacterial toxins in S. aureus collected from bloodstream infections. Sixty different S. aureus isolates were obtained from blood cultures of patients who were admitted to a Teaching Hospital in Tianjin from January 2006 to August 2011. The susceptibility of the isolates to 16 antibiotics was tested. Methicillin-resistant S. aureus (MRSA) was identified using the disk diffusion method with cefoxitin. PCR was used to detect genes that encode the staphylococcal enterotoxins, Panton-Valentine leukocidin, toxic shock syndrome toxin 1 and erythromycin ribosome methylase. Molecular analysis of the MRSA strains was done using pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome mec (SCCmec) typing. The positivity rates of mecA, ermA, ermB, and ermC in the isolates were 13/60, 10/60, 18/60, and 18/60, respectively. Among the 60 isolates, 30 harbored enterotoxin genes, with sea as the most frequent toxin gene (33%), followed by sec (15%), sed (12%), and seb (5%). The see and tst genes were not found in any of the isolates. The pvl gene was detected in four strains. Eleven MRSA isolates were of the SCCmec type III; two MRSA isolates could not be determined through SCCmec typing. PFGE analysis of the 13 MRSA isolates produced 8 distinct pulsotypes. Virulence genes and erythromycin ribosome methylase genes were highly prevalent in these isolates. The PFGE results demonstrated that the MRSA spread through cloning, mainly involving SCCmec type III.

Establishment and characterization of two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus and derived from nasopharyngeal carcinomas.

Two epithelial tumor cell lines were established from biopsy specimens of 2 nasopharyngeal carcinomas (NPC) and designated HNE-1 and HONE-1. Uncloned HNE-1 cells were found to be Epstein-Barr virus (EBV) DNA-positive when examined by Southern blot analysis up to passage 35, after which the EBV genome could no longer be detected. A similar loss of EBV DNA took place in uncloned HONE-1 cells. However, HONE-1 clone 40 cells are still EBV DNA-positive up to passage 42 thus far and cell cultures contain 85-90% EBV nuclear antigen (EBNA)-positive cells. The HNE-1 cell line has been passaged more than 100 times and the uncloned HONE-1 cells more than 90 times. The tumorigenicity of the HNE-1 and HONE-1 cells was demonstrated by tumor induction in nude mice. Karyotypic analysis of the HNE-1 cells demonstrated an aneuploidy with a modal chromosomal number of 74 at passages 5 and 101 at passage 20; 18 marker chromosomes were identified. We have continued to map the EBV genome latently associated with the HNE-1 and HONE-1 cells using the Bam HI, EcoRI or Hind III restriction enzymes. Using EcoRI fragments A-K as probes, we found that HNE-1 EBV DNA is different from B95-8 and HR-1 EBV DNA in the EcoRI-C region. The Bam HI map for HONE-1 EBV DNA is very similar to the B95-8 map; it contains the Bam HI-Y fragment but without Bam HI B' and WI'. Differences were observed between HONE-1 EBV DNA and B95-8 DNA using the Hind III restriction enzyme. There was no evidence of spontaneous expression of the latent EBV genome in HNE-1 cells, and attempts to induce replication of the latent EBV genome and rescue infectious virus have failed, suggesting a tightly restricted virus genome.

Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas.

Two epithelial tumor cell lines were established from biopsy specimens of nasopharyngeal carcinomas (NPC). The specimens were taken from poorly differentiated squamous cell carcinomas of the nasopharynx. The tissues were prepared for cell culture and eventually two continuous epithelial cell lines were obtained and designated HONE-1 and HNE-1. Light and electron microscopic examination of these two cell lines demonstrated cells with an epithelial morphology including the presence of desmosomes. The HNE-1 cell line has been passaged more than 100 times and the HONE-1 cell line has been passaged more than 90 times. It was found that early-passage uncloned HNE-1 cells (passage 23) could be superinfected with the B95-8 and NPC-EBV isolates as demonstrated by the induction of Epstein-Barr virus (EBV)-specific early antigen(s) in a small percentage of the cells; HONE-1 cells could also be superinfected with EBV. Southern blot analysis detected EBV DNA in samples from uncloned HNE-1 cells at passages 12, 17, 21, 27, and 35. However, by passage 45, EBV DNA could no longer be detected in HNE-1 cells by Southern blot analysis. The EBV genome was detected in parental HONE-1 cells at subculture 9 and in clone 40 cells up to passage 40 thus far. When HNE-1 cells were examined for the expression of the EBV-encoded nuclear antigen (EBNA) at passage 12, only about 10% of the cells were found to be positive. The percentage of EBNA-positive HNE-1 cells decreased as the cells were passaged. A similar loss of EBNA was observed in uncloned HONE-1 cells, but not in HONE-1 clone 40 cells. In clone 40, which has been passaged 40 times thus far, 85-90% of the cells are still EBNA-positive. The data suggest that EBV genome-positive HNE-1 and HONE-1 cells were lost as the cells were cultivated in vitro and that cloning the cells at an early passage level may be critical in maintaining EBV genome-positive epithelial NPC cells. These EBV genome-positive epithelial NPC cell lines will be useful for studying the association of EBV and NPC.

[Immunocytochemical and morphologic features of poorly differentiated adenocarcinoma of the nasopharynx].

Poorly differentiated adenocarcinoma of the nasopharynx is not rare. It comprises 5% of all nasopharyngeal carcinomas. In this paper, specimens of 41 cases of poorly differentiated adenocarcinoma of the nasopharynx were studied. The microscopic findings have the tendency to form glandular or duct-like structures, or a specific "cerebriform" appearance, AB-PAS stain was positive. In addition to the common features of adenocarcinoma (cancer cells vary in size, with large, round central nuclei, enlarged conspicuous nucleoli), a specific feature that the nuclei of cancer cells were 1-2 times larger than those of normal cells was seen in smear. Electron microscopic observation revealed that the cytoplasm of the cancer cells contained numerous mitochondria, RER, developed Golgi apparatus and some secretory granules. Immunocytochemical studies proved that it was moderately positive for immunostain of low molecular weight keratin protein (K10,11), but was negative for keratin (K) it is different from poorly differentiated squamous cell carcinoma and vesicular nuclear cell carcinoma, of which were strongly positive or partially positive for keratin. The main points of differential diagnosis for these carcinomas are elucidated.