The 3-Dimensional Intelligent Structured Light Technique: A New Registration Method in Stereotactic Neurosurgery.

BACKGROUND AND OBJECTIVES: Surface-based facial scanning registration emerged as an essential registration method in the robot-assisted neuronavigation surgery, providing a marker-free way to align a patient's facial surface with the imaging data. The 3-dimensional (3D) structured light was developed as an advanced registration method based on surface-based facial scanning registration. We aspire to introduce the 3D structured light as a new registration method in the procedure of the robot-assisted neurosurgery and assess the accuracy, efficiency, and safety of this method by analyzing the relative operative results. METHODS: We analyzed the results of 47 patients who underwent Ommaya reservoir implantation (n = 17) and stereotactic biopsy (n = 30) assisted by 3D structured light at our hospital from January 2022 to May 2023. The accuracy and additional operative results were analyzed. RESULTS: For the Ommaya reservoir implantation, the target point error was 3.2 ± 2.2 mm and the entry point error was 3.3 ± 2.4 mm, while the operation duration was 35.8 ± 8.3 minutes. For the stereotactic biopsy, the target point error was 2.3 ± 1.3 mm and the entry point error was 2.7 ± 1.2 mm, while the operation duration was 24.5 ± 6.3 minutes. CONCLUSION: The 3D structured light technique reduces the patients' discomfort and offers the advantage of a simpler procedure, which can improve the clinical efficiency with the sufficient accuracy and safety to meet the clinical requirements of the puncture and navigation.

Genetic Intratumor Heterogeneity Remodels the Immune Microenvironment and Induces Immune Evasion in Brain Metastasis of Lung Cancer.

INTRODUCTION: Brain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown. METHODS: Whole-exome sequencing and RNA sequencing were performed on 30 matched brain metastasis, primary lung adenocarcinoma, and normal tissues. Data from The Cancer Genome Atlas primary lung adenocarcinoma cohort, including multiplex immunofluorescence, were used to support the findings of bioinformatics analysis. RESULTS: Our study highlights the key role of intratumor heterogeneity of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency or other somatic copy number alteration-associated mutation mechanisms, leading to increased genomic instability and genomic complexity. We further proposed a selection model of brain metastatic evolution in which intratumor heterogeneity drives immune remodeling, leading to immune escape through different mechanisms under local immune pressure. CONCLUSIONS: Our findings provide novel insights into the metastatic process and immune escape mechanisms of brain metastasis and pave the way for precise immunotherapeutic strategies for patients with lung cancer with brain metastasis.

Prognostic model of hepatocellular carcinoma based on cancer grade.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. With highly invasive biological characteristics and a lack of obvious clinical manifestations, HCC usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary HCC are still unclear. AIM: To select the characteristic genes that are significantly associated with the prognosis of HCC patients and construct a prognosis model of this malignancy. METHODS: By comparing the gene expression levels of patients with different cancer grades of HCC, we screened out differentially expressed genes associated with tumour grade. By protein-protein interaction (PPI) network analysis, we obtained the top 2 PPI networks and hub genes from these differentially expressed genes. By using least absolute shrinkage and selection operator Cox regression, 13 prognostic genes were selected for feature extraction, and a prognostic risk model of HCC was established. RESULTS: The model had significant prognostic ability in HCC. We also analysed the biological functions of these prognostic genes. CONCLUSION: By comparing the gene profiles of patients with different stages of HCC, We have constructed a prognosis model consisting of 13 genes that have important prognostic value. This model has good application value and can be explained clinically.

Trends and determinants of place of death among Chinese lymphoma patients: a population-based study from 2013-2021.

Limited research exists on factors influencing the place of death (POD) or hospital deaths among lymphoma patients in China, despite the country's significant burden of lymphoid neoplasms. This study aimed to describe the distribution of POD among lymphoma patients and identify the factors associated with hospital lymphoma deaths to provide evidence for developing targeted healthcare policies. Data in this study were obtained from the National Mortality Surveillance System (NMSS). The distribution of POD among individuals who died from lymphoma was analyzed, and factors influencing the choice of dying in the hospital were examined. Chi-square test was employed to analyze the differences in characteristic distributions. Multilevel logistic regression analysis was identify the relationship between hospital deaths due to lymphoma and individual factors, as well as socioeconomic contextual variables. During 2013-2021, there were 66772 lymphoma deaths reported by the NMSS, including 44327 patients (66.39%) who died at home and 21211 (31.77%) died in the hospital. Female patients, those had a higher level of educational attainment, retired individuals, those died of non-Hodgkin lymphoma, residents of urban areas, patients between the ages of 0 and 14, and unmarried individuals had a higher probability of dying in hospitals. Improving health care providers' understanding of palliative care for cancer patients and prioritizing accessible services are essential to enhance the quality of end-of-life care. These approaches ensure the equitable allocation of healthcare resources and provide diverse options for minorities with specific preferences regarding end-of-life care.

The influence of Tai Chi exercise on the subjective well-being in the aged: the mediating role of physical fitness and cognitive function.

This study investigated the effects of Tai Chi exercise on subjective well-being in the aged. The participants were randomly assigned to an experimental group or a control group. The experimental group received 12-week Tai Chi exercise while the control group maintain their original living habits. The participants' subjective well-being, physical fitness, self-control, and executive function were measured at baseline and after 12 weeks of Tai Chi exercise. Results: (1) Tai Chi exercise can positively affect the subjective well-being of the aged (F(1,78) = 37.699, p < 0.001); (2) Tai Chi exercise could affect the subjective well-being in the aged through the independent intermediary of physical fitness (95% CI=[0.115, 0.485]) and self-control (95% CI=[0.109, 0.433]); (3) Tai Chi exercise could indirectly affect the subjective well-being in the aged through the chain mediation of executive function and self-control (95% CI=[0.009, 0.104]). This study provides valuable insights into the potential benefits of Tai Chi exercise for subjective well-being in the aged.

The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment. METHODS: We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model. RESULTS: We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC. CONCLUSIONS: Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

Bevacizumab reduces peritumoral brain edema in lung cancer brain metastases after radiotherapy.

BACKGROUND: The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. METHODS: A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow-up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression-free survival (PFS) were compared between the two groups. RESULTS: The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1-2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). CONCLUSION: Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.

Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.

BACKGROUND: The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. METHODS: The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. RESULTS: A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations. CONCLUSIONS: Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.

Why are hedonists less happy than eudaimonists? The chain mediating role of goal conflict and mixed emotions.

Introduction: Human motivation for happiness involves two main orientations of hedonia and eudaimonia. Numerous studies have shown that hedonic motivation has a much smaller effect on happiness outcomes than eudaimonic motivation, but little is known about the reasons for this. According to the Self-Determination Theory and the Levels of Valence Model, this may be related to the different goal conflicts and mixed emotions elicited by the two motivations. To demonstrate this, the study examined the mediating effect of the above two variables between happiness motivation and life satisfaction. Furthermore, it explained why hedonists are less happy than eudaimonists by comparing the two happiness motivations in terms of their respective path effects. Methods: The study randomly selected 788 college students from 13 different provinces of China to examine the relationships between hedonic motivation, eudaimonic motivation, goal conflict, mixed emotions, and life satisfaction. Results: The result showed that (1) the direct effect of hedonic motivation on life satisfaction was marginally significant, and the effect size was much smaller than that of eudaimonic motivation. (2) The direct and indirect effects of hedonic motivation were the opposite, with a large suppressing effect. In contrast, all paths of eudaimonic motivation positively affected life satisfaction. (3) Hedonic motivation negatively influenced life satisfaction through mixed emotions and the chain mediating effect of goal conflict and mixed emotions, whereas eudaimonic motivation positively influenced life satisfaction through these two mediating paths. (4) The effects on all paths of hedonic motivation were significantly smaller than those of eudaimonic motivation, except for the path mediated by goal conflict. Discussion: This study explains why hedonists are less happy than eudaimonists from the perspective of goal pursuit, emphasizes the critical role of differences in goal pursuit state and experience between happiness motivation and life satisfaction, and provides new ideas for the study of the influence mechanism of happiness motivation. At the same time, the deficiencies of hedonic motivation and the advantages of eudaimonic motivation presented by the study provide directions for cultivating happiness motivation for adolescents in the practice field.

Academics-Athletics Conflict and College Athletes' Well-Being: The Mediating Effect of Negative Emotions and the Moderating Effect of Life Motivation.

For college athletes who perform dual roles (student and athlete), the academics-athletics conflict is inevitable in daily life. Although existing studies have focused on the adverse effects of this conflict on the well-being of college athletes, they have not yet determined the underlying mechanism and effective measures to alleviate it. To explore the underlying mechanism of academics-athletics conflict, which affects the well-being of college athletes, we constructed a moderated mediating model to examine the critical role of negative emotions and life motivation in the relationship between them. The study randomly selected 802 college athletes from China to examine the relationships between academics-athletics conflict, negative emotions, eudaimonic motives, hedonic motives, and life satisfaction. The results showed that (1) negative emotions played an important mediating role between academics-athletics conflict and college athletes' life satisfaction, with more than 79% of the effect of academics-athletics conflict being achieved through negative emotions. (2) Eudaimonic motives significantly moderated the first half of the mediation path of negative emotions between academics-athletics conflict and life satisfaction. Individuals with high eudaimonic motives experienced fewer negative emotions in the medium and weak conflict conditions. (3) Hedonic motives had a significant moderating effect on the second half of the mediation path. Individuals with high hedonic motives had greater life satisfaction across negative emotion conditions. This study provides important insights for a comprehensive understanding and in-depth study of the relationship between conflict and the well-being of college athletes, as well as a reference for the quality-of-life enhancement and motivation development for college athletes.

Developmental Trajectory of Depressive Symptoms in Chinese College Students: Latent Classes and Gender Effect.

Depressive symptoms are prevalent in Chinese college students, but little is known about the heterogeneity in the developmental trajectory of depressive symptoms in China. This study examined heterogeneity in the development of depressive symptoms and examined the effect of gender on the developmental trajectories over a 14-month period among Chinese college students (N = 1163, mean age 20.18, 80.31% female). Three different trajectories, moderate-increasing, high-stable and low-stable, captured the heterogeneity in the development of depressive symptoms. Gender showed significant influence on class membership. Relative to the moderate-increasing class, males emerged as significantly more likely than females to be found in the low-stable class (odds ratio (OR) = 2.73, 95% CI = (1.21, 6.13), p = 0.015) and the high-stable class (OR = 5.10, 95% CI = (1.12, 23.18), p = 0.035). The results provide additional evidence for the conclusion that the trajectories of depressive symptoms are heterogeneous with Chinese samples. Moreover, cultural difference should be paid more attention to when examining the effect of gender and other predictors of the trajectories of depressive symptoms.

Relapsed/refractory classical Hodgkin lymphoma effectively treated with low-dose decitabine plus tislelizumab: A case report.

BACKGROUND: Academic studies have proved that anti-programmed death-1 (PD-1) monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma (cHL). However, most patients ultimately experienced failure or resistance. It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL. The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/ refractory cHL patients with prior PD-1 inhibitor exposure. CASE SUMMARY: The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission. Histological analysis of lymph node biopsy was suggestive of cHL. The patient experienced failure of eight lines of therapy, including multiple cycles of chemotherapy, PD-1 blockade, and anti-CD47 antibody therapy. Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab. The patient had been followed for 11.5 mo until March 2, 2021, and no progressive enlargement of the tumor was observed. CONCLUSION: The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/ refractory cHL. The therapeutic effect of this strategy needs to be further assessed.

Implications of driver genes associated with a high tumor mutation burden identified using next-generation sequencing on immunotherapy in hepatocellular carcinoma.

Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multiple types of tumor, including HCC. Specific driver gene mutations may be indicative of a high TMB (TMB-H) and analysis of such mutations may provide novel insights into the underlying mechanisms of TMB-H and potential therapeutic strategies. In the present study, a hybridization-capture method was used to target 1.45 Mb of the genomic sequence (coding sequence, 1 Mb), analyzing the somatic mutation landscape of 81 HCC tumor samples. Mutations in five genes were significantly associated with TMB-H, including mutations in tumor protein 53 (TP53), Catenin®1 (CTNNB1), AT-rich interactive domain-containing protein 1A (ARID1A), myeloid/lymphoid or mixed-lineage leukemia (MLL) and nuclear receptor co-repressor 1 (NCOR1). Further analysis using The Cancer Genome Atlas Liver Hepatocellular Carcinoma database showed that TP53, CTNNB1 and MLL mutations were positively correlated with TMB-H. Meanwhile, mutations in ARID1A, TP53 and MLL were associated with poor overall survival of patients with HCC. Overall, TMB-H and associated driver gene mutations may have potential as predictive biomarkers of ICB therapy efficacy for treatment of patients with HCC.

Cytoplasmic expression of estrogen receptor ß may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma.

There is growing evidence that estrogen receptors (ER) are expressed in lung cancer cells, and are able to interact with the epidermal growth factor receptor (EGFR) signaling pathway. However, data on the association between cytoplasmic ER expression and the response to EGFR-tyrosine kinase inhibitors (TKI) treatment are limited. The aim of the present study was to investigate the associations between ERα/ERß expression and EGFR mutational status and response to TKI treatment in metastatic lung adenocarcinoma. A retrospective study of 126 consecutive patients with lung adenocarcinoma who were diagnosed with stage IV disease and had received EGFR-TKI treatment was conducted. ER expression was detected by immunohistochemistry. EGFR and GTPase KRas (KRAS) mutational statuses were evaluated by denaturing high performance liquid chromatography and PCR-restriction fragment length polymorphism, respectively. In the overall cohort of 126 lung adenocarcinoma samples analyzed, ERα expression in the nucleus of tumor cells was identified in 17 (18.9%) patients, whereas ERß expression was identified in the nucleus (22/126, 17.5%) and cytoplasm (17/126, 13.5%). The nuclear expression of ERß was positively associated with the degree of tumor differentiation (P=0.010). EGFR-sensitizing mutations were significantly associated with improved objective response rates (ORR), disease control rates (DCR), median progression-free survival (mPFS) and median overall survival (mOS) (P<0.001; P<0.001; P=0.003; and P=0.026, respectively). Patients with cytoplasmic ERß expression exhibited non-significant poorer ORR, DCR, mPFS and mOS compared with patients without cytoplasmic ERß expression (P=0.082; P=0.106; P=0.084; and P=0.119, respectively). However, the significant decrease of ORR, DCR and mPFS was observed in patients with coexisting cytoplasmic ERß expression and EGFR-sensitizing mutations (P=0.030; P=0.009; and P=0.018, respectively) in comparison with the subgroup with EGFR sensitizing mutations but negative expression of cytoplasmic ERß. A trend towards shorter mOS was also observed in patients with coexisting cytoplasmic ERß expression and EGFR-sensitizing mutations (P=0.071). No KRAS mutations were identified in patients with cytoplasmic ERß expression. Subsequent to adjusting for sex, smoking status and EGFR mutation status, the Cox repression analysis indicated that cytoplasmic expression of ERß was a negative independent predictor for mPFS in the whole patient cohort (HR=1.870; 95% confidence interval 1.058-3.305; P=0.031). Cytoplasmic ERß expression was negatively correlated with the efficacy of EGFR-TKI treatment for metastatic lung adenocarcinoma, particularly for patients with coexisting cytoplasmic ERß expression and EGFR-sensitizing mutations. Cytoplasmic ERß may be a promising marker to predict the outcome of EGFR-TKI treatment.

SMURF1 facilitates estrogen receptor ɑ signaling in breast cancer cells.

BACKGROUND: Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. METHODS: SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR. WST-1 assay was used to measure cell viability; the xeno-graft tumor model were used for in vivo study. RNA sequencing was analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling was accomplished with luciferase assays, real-time RT-PCR and Western blotting. Protein stability assay and ubiquitin assay was used to detect ER alpha protein degradation. Immuno-precipitation based assays were used to detect the interaction domain between ER alpha and SMURF1. The ubiquitin-based Immuno-precipitation based assays were used to detect the specific ubiquitination manner happened on ER alpha. RESULTS: Here, we identify the E3 ligase SMURF1 facilitates ER alpha signaling. We show that depletion SMURF1 decreases ER alpha positive cell proliferation in vitro and in vivo. SMURF1 depletion based RNA-sequence data shows SMURF1 is necessary for ER alpha target gene expression in the transcriptomic scale. Immunoprecipitation indicates that SMURF1 associates with the N-terminal of ER alpha in the cytoplasm via its HECT domain. SMURF1 increases ER alpha stability, possibly by inhibiting K48-specific poly-ubiquitination process on ER alpha protein. Interestingly, SMURF1 expression could be induced via estradiol treatment. CONCLUSIONS: Our study reveals a novel positive feedback between SMURF1 and ER alpha signaling in supporting breast cancer growth. Targeting SMURF1 could be one promising strategy for ER alpha positive breast cancer treatment.

Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

BACKGROUND: Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. METHODS: Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. RESULTS: Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P < 0.05. Using 8.78 ng/mL as the cut off value, serum AFP level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P < 0.05. There was significant difference between the time of diagnosis with HCC to serum AFP level elevation and the time of AFP elevation to death, P < 0.05. CONCLUSION: Prognosis of HCC patients with normal AFP level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS.

[Recent Advances in Association of Estrogen and Non-small Cell Lung Cancer].

Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is one of the most prevalent cancers and the most leading cause of cancer mortality. Despite recent improvements in its treatment, the prognosis remains dismal. Previous studies have clearly proved that estrogen and estrogen receptors (ER) are involve in the pathogenesis and development of lung cancer. More and more evidences showed antiestrogen therapy may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor. We will review recent progress in the function of estrogen in NSCLC and the treatment based on the ER signaling pathways for NSCLC in this article.

ERß localization influenced outcomes of EGFR-TKI treatment in NSCLC patients with EGFR mutations.

Effects of estrogen receptorß (ERß) localization on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) are unknown. First, we analyzed the relationship between ERß localization determined by immunohistochemistry and EGFR-TKI outcomes in 184 patients with advanced NSCLC and found that ERß expression localized in the cytoplasm and/or nucleus. The frequency of cytoplasmic ERß (c-ERß) and nuclear ERß (n-ERß) co-expression was 12% (22/184). C-ERß and n-ERß co-expression was correlated with poor median progression-free survival compared to patients without co-expression. In subsequent in vitro experiments, PC9 cells transfected with ERß isoform1 (ERß1, strong expression of both c-ERß and n-ERß) were more resistant to gefitinib than PC9 cells transfected with ERß isoform2 or 5 (ERß2 or ERß5, strong expression of ERß in cytoplasm but not nucleus). Resistance was identified due to interactions between ERß1 and other isoforms, and mediated by activation of non-genomic pathways. Moreover, gefitinib resistance was reversed by a combination treatment with gefitinib and fulvestrant, both in cell lines and in one NSCLC patient. These results suggested that c-ERß and n-ERß co-expression was a potential molecular indicator of EGFR-TKI resistance, which might be overcome by combining EGFR-TKI and ER antagonist.

PIK3CA mutation in Chinese patients with lung squamous cell carcinoma.

OBJECTIVE: To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma (LSCC) and explore their relationship with clinicopathological profiles. METHODS: Tumor samples from 123 cases of LSCC were included in this study. PIK3CA mutations in exon 9 and 20 were screened by pyrosequencing and confirmed by clone sequencing or amplification refractory mutation system (ARMS). Denaturing performance liquid chromatography (DHPLC) was employed for evaluation of EGFR mutation in exon 19, 21 and KRAS mutation. RESULTS: PIK3CA mutations were found in 3 (2.4%) patients. The mutation type included E545K, E452Q and H1047R. Of these three patients, one coupled with EGFR mutation, and the other two coupled with PIK3CA amplification. All the three patients shared the same clinicopathologic characteristics: male, less than 60 years old, had smoke history, stage III and carried wild-type KRAS. CONCLUSIONS: The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.

Toxic effects of Microcystis cell extracts on the reproductive system of male mice.

In this paper, the reproductive toxicity of male mice treated with Microcystis aeruginosa cell extracts containing microcystins was examined. In contrast to the control group, male mice exposed intraperitoneally to 3.33 or 6.67 microg microcystins/kg body weight for 14 days had decreased mean body weight, and the mean absolute weight of the testes and epididymides was decreased. However, the mean relative weight of the testes increased compared to the controls. In addition, histological examination of microcystin-treated mice indicated that the testes were damaged and the space between the seminiferous tubules was more pronounced compared to control mice. The quality of mature sperm in the seminiferous tubules was also decreased in treated mice compared with the control group. Further studies showed that motility and viability of the sperm from microcystin-treated mice were reduced, but no significant difference was found in the concentration and abnormality of the sperm from treated mice compared to the control. This study indicated that microcystins had numerous toxic effects on the reproductive system of male mice.