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Background: This study attempted to examine the discordance between family caregivers and cancer patients in their poor-prognosis disclosure preferences in mainland China and then ascertained the associations between quality of life (QoL), perceived stress, and poor-prognosis disclosure preferences.Methods: Six hundred fifty-one pairs of inpatients and their matched caregivers (participation rate = 92.2%) were recruited in this cross-sectional survey. A set of paired self-administered questionnaires were completed independently by patient-caregiver dyads.Results: Fewer family caregivers than cancer patients felt that poor prognosis should be disclosed to patients (61.2% vs. 90.0%, p < 0.001). Patients' positive poor-prognosis disclosure preference was associated with patients' better QoL (p < 0.05) and caregivers' reduced perceived stress levels (p = 0.013). However, caregivers' poor-prognosis disclosure preference correlated only with their own physical state (p = 0.028). Moreover, the caregivers who concurred with patients in positive poor-prognosis disclosure preference were more likely to experience a better QoL (p < 0.05) and lower perceived stress levels (p = 0.048) in the III-IV stage subgroup.Conclusions: There was a significant discrepancy in poor-prognosis disclosure preference between cancer patients and caregivers in China. The caregivers' preference of concealing poor prognosis from patients was not related to cancer patients' QoL or perceived stress. In addition, caregivers had better QoL and lower stress levels when they held the same positive poor-prognosis disclosure preference as the patients. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The Sm3+-doped low-phonon-energy (LPE) Ge–Ga–Se–CsI glasses were studied. Upon excitation at 980nm diode laser, intense 1.25 and 1.49μm near-infrared fluorescence bands with broad full width at half maximum (FWHM) of 49 and 53nm were observed, respectively. About 180–300μs fluorescence lifetimes were obtained for the 1.49μm emission. The thermal properties and structure of glasses were investigated by differential thermal analysis (DTA) and Raman spectra, respectively. Spectroscopic characteristics of the optical transitions have been calculated by using the Judd–Ofelt theory and evaluated for excited levels. [Copyright &y& Elsevier]

Abstract: Background: LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods: We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results: Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32–6.72 and 1.01–4.94, P =0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24–4.28 and 1.11–3.62, and P =0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy. Conclusion: Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Developing bioactive axial ligands ligated platinum(IV) complexes with advantages over monotherapy and drug combinations is an efficient strategy to ameliorate the clinical defects of platinum(II) drugs. In this article, a series of 4-amino-quinazoline moieties (privileged pharmacophores of well-studied EGFR inhhibitors) ligated platinum(IV) were synthesized and evaluated for their anticancer activities. Among the complex, 17b demonstrated higher cytotoxicity against the tested lung cancer cells (including CDDP-resistant A549/CDDP cells) while lower cytotoxicity toward human normal cells than Oxaliplatin (Oxa) or cisplatin (CDDP). Mechanistic investigation demonstrated that the enhanced intracellular uptake of 17b efficiently elevated the of reactive oxygen species levels by 6.1 times more than Oxa. Detailed mechanisms of overcoming CDDP resistance revealed that 17b significantly induced apoptosis via inducing severe DNA damage, disturbing mitochondrial transmembrane potentials, efficiently disturbing EGFR-PI3K-Akt signaling transduction and activating a mitochondria-dependent apoptosis pathway. Besides, 17b significantly inhibited migration and invasion in A549/CDDP cells. In vivo tests exhibited that 17b obtained superior antitumor effect and attenuated systemic toxicity in A549/CDDP xenografts. All these results emphasized that the antitumor action of 17b differed from that of. classical platinum(II) drugs and provided a novel practical method to overcome CDDP resistance in lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Platinum(II)-based drugs play an important role in many chemotherapeutic protocols, but their further clinical applications are hindered by the development of drug resistance and serious side effects. Therefore, to reverse cisplatin (CDDP) resistance in tandem with reduced side effects, nine novel platinum(IV) complexes modified with key pharmacophore of Olaparib were synthesized and evaluated for biological activities. Among them, the optimal complex 8-2 showed good inhibitory activity against PARP-1 and superior anticancer effects over CDDP on parental (MDA-MB-231, IC 50  = 1.13 μM) and CDDP -resistant triple-negative breast cancer (TNBC) cell line (MDA-MB-231/CDDP, IC 50  = 1.72 μM). Detailed mechanisms revealed that compared with Olaparib and CDDP, the enhanced intracellular accumulation of 8-2 could efficiently reverse CDDP resistance in MDA-MB-231/CDDP cells via inhibiting DNA repair-associated mechanisms, enhancing DNA damage, and activating mitochondrion-dependent apoptosis pathway. Furthermore, 8-2 obtained higher tumor growth inhibition rate (64.1 %) than CDDP (26.5 %) in MDA-MB-231/CDDP xenografts, but it did not induce significant toxicity in vivo and in intro, making it a potential drug candidate for the treatment of TNBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment., (© 2022. Higher Education Press.)

Hepatocellular carcinoma (HCC) is the most common neoplasm and the major cause of cancer-associated death worldwide. The high mortality rate of HCC is mainly attributed to its widespread prevalence and the lack of effective treatment. Immunotherapy as a promising, innovative approach has revolutionised the treatment of solid tumours. However, owing to the heterogeneity and complex tumour microenvironment of HCC, an efficient biomarker for immunotherapy has yet to be identified. We investigated the role of immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in patients with HCC from The Cancer Genome Atlas (TCGA) database. Spearman correlation, univariate and multivariate Cox, and lasso regression analyses were utilised to screen lncRNAs associated with prognosis. Four lncRNAs were filtered out to develop an immune-associated lncRNA prognostic signature in TCGA training as well as validation cohorts. Patients with HCC were then categorised into low- and high-risk groups according to the median value of the risk scores to evaluate the ability of the prognostic model between training and validation cohorts. A nomogram (based on risk score and stage) was constructed to appraise the general overall survival (OS) of patients with HCC. Differences in immune cell infiltration, immune checkpoint inhibitor (ICI) treatment response, gene mutation, and drug sensitivity were observed between the two groups. Thus, the lncRNA prognostic signature can serve as a sensitive prognostic biomarker with potential in individualised immunotherapy for HCC patients., (© 2022. The Author(s).)

Background: Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors., Methods: HCCDB, CCLE, HPA and LinkedOmics online databases were used to explore the expression of CPNE1 gene and analyze the co-expression network of CPNE1 in hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis and regulators of CPNE1 networks in LIHC. HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and Hep3B cell was selected to construct CPNE1 overexpression cell line by transfection with plasmid. The effect of CPNE1 on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database and GSEA., Results: CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. Knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. Overexpression of CPNE1 gene showed the opposite results. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells (P < 0.001). GSEA results also showed that CPNE1 of LIHC was involved in some immune response regulating signaling pathways., Conclusions: Our study firstly found the expression of CPNE1 was significantly higher in LIHC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. In addition, we identified the possible mechanism by which CPNE1 functioned in LIHC. CPNE1 influenced AKT/P53 pathway activation and LIHC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in LIHC., (© 2022. The Author(s).)

Systematic toxicity and drug resistance significantly limited FDA-approved platinum drugs for further clinical applications. In order to reverse the resistance (MDR) and enhance their anticancer efficiency, four Pt(IV) complexes (12-15) conjugating with P-glycoprotein (P-gp) inhibitors were designed and synthesized. Among them, complex 14 (IC 50  = 3.37 μM) efficiently reversed cisplatin resistance in SGC-7901/CDDP cell line and increased selectivity index (6.9) against normal HL-7702 cell line. Detailed mechanisms in SGC-7901/CDDP cells assays revealed that complex 14 efficiently induced apoptosis via down-regulating expression of P-gp for enhanced intracellular uptake of platinum, arrested cells at G2/M phase, induced DNA damage and initiated mitochondrial apoptosis pathway. Further in vivo studies demonstrated that the enhanced accumulation of complex 14 contributed to tumor inhibition of 75.6% in SGC-7901/CDDP xenografts, which was much higher than cisplatin (25.9%) and oxaliplatin (43%). Moreover, the low systematic toxicity made 14 a potential novel P-gp-mediated MDR modulator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Sorafenib has been confirmed as an effective drug in advanced renal cell carcinoma (RCC). This study aimed to evaluate the long-term efficacy and safety of sorafenib in ethnic Chinese patients with advanced RCC, and to develop optimal treatment strategies for Asian patients. Between May 2006 and August 2011, 30 patients with advanced RCC were treated with sorafenib in the Oncology Center, Tongji Hospital. All 30 patients received continuous treatment with 400 mg of sorafenib orally twice daily until disease progression or intolerable toxicities or mortality occurred. Dose reduction to 600 mg daily or even less was required if toxicities of grade 3 or 4 occurred. Patients were assessed for tumor response, progression-free survival (PFS), overall survival (OS) and drug-related toxicities. The median follow-up time was 58 weeks (range, 12-270). Among the 30 patients, 1 patient had complete remission (CR 3.3%), 4 patients had partial remission (PR 13.3%), 19 patients had stable disease (SD 63.3%) and 6 patients had disease progression (PD 20%). The disease control rate (DCR, CR+PR+SD) was 80%, the median PFS time was 14 months, and the median OS time was 16 months. Only 1 patient discontinued sorafenib treatment permanently due to severe toxicities. Dose reduction or interruption was required in 12 patients (40%) who developed adverse events of grade 3 or 4. Seven of these patients tolerated the dose of 600 mg per day well, and experienced clinical benefit. The Kaplan-Meier method and log-rank test revealed that the Memorial Sloan-Kettering Cancer Center (MSKCC) status was a prognostic factor for PFS and OS in advanced RCC. The long-term efficacy and safety of sorafenib were confirmed in Chinese advanced RCC patients who showed an even greater benefit in PFS. The findings of this study indicate that a dose of 600 mg instead of 400 mg per day may be an optimal choice for Asian patients when a reduction of the initial dose is required.

DNA-dependent protein kinase (DNA-PK), including Ku80, Ku70 and DNA-PK catalytic subunit (DNA-PKcs), is the key protein in non-homologous end-joining (NHEJ) after DNA double-strand breaks (DSBs) appear. In this study, small hairpin interfering RNAs (siRNAs) targeting Ku80 and DNA- PKcs were used both individually and in combination, to explore the effects of these DSB proteins on HeLa cell functional changes after X-ray irradiation. HeLa cells co-transfected with Ku80-siRNA and DNA-PKcs-siRNA were more radiosensitive than the ones transfected individually. HeLa in the absence of Ku80 and pretreated with LY294002, a chemically specific PI 3-kinase inhibitor, resulted in cells that were even more sensitive to X-rays than HeLa/Ku80-siRNA transfected with DNA- PKcs-siRNA. The cells inhibited by Ku80 either individually or in combination with DNA-PKcs showed cell accumulation in the G2/M phase 48 h post-irradiation, similarly to control cells. However, cells transfected with DNA-PKcs-siRNA or pretreated with LY294002 had a prolonged G2/M delay, suggesting the accumulation of significant un-repaired DNA damage following inhibition of DSB repair proteins. In conclusion, these data indicate that the role of Ku80 in DSB repair could be compensated by other DSB repair proteins; co-inhibition would be a suitable strategy to enhance the radiosensitivity of cancer cells.

In order to investigate the effects of short hairpin RNA (shRNA) on the expression of Survivin, cell cycle and cell proliferation in MCF-7 cells, using a pEGFP vector which contained a U6 promoter shRNA plasmid targeted against survivin was constructed and transfected into MCF-7 cells. The change of the expression of Survivin and cell proliferation rates were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and MTT methods respectively. The change of cell cycle after transfection was analyzed by flow cytometry. The results indicated that the recombinant plasmid containing Survivin shRNA was constructed successfully, which could suppress the expression of Survivin at mRNA and protein level. The growth of MCF-7 cells was arrested in G1 phase of the cell cycle and the proliferation activity was suppressed after transfection. It was concluded that Survivin shRNA plasmid could knock down the expression of Survivin in MCF-7 cells specifically. In addition, Survivin shRNA plasmid could lead to G1 arrest and inhibit the proliferation of MCF-7 cells, which suggested that Survivin shRNA might be used as a new therapeutic method for breast cancer.