APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer.

Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested.

Clinical application status and prospect of the combined anti-tumor strategy of ablation and immunotherapy.

Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy.

Calcium-Loaded Municipal Sludge-Biochar as an Efficient and Stable Catalyst for Biodiesel Production from Vegetable Oil.

In this contribution, biochar from municipal sludge was used as a novel matrix for the synthesis of a series of calcium-based heterogeneous catalysts toward biodiesel production. Their catalytic activity was investigated in terms of catalyst loading and calcination temperature during preparation, in addition to the transesterification parameters including the methanol/oil molar ratio, reaction time, and catalyst amount. The highest biodiesel yield up to 93.77% was achieved with the 30Ca/A-SBC-700, and it maintained as high as 84.9% even after 10 cycles of a consecutively alternating catalysis and regeneration process. It was revealed that the porous municipal sludge biochar and autologous SiO2 were accountable for the superior stability of the present catalyst. This work may provide a new path to value-added valorization of sludge waste and also a renewable and efficient catalyst for biodiesel production at a low cost.

[Preparation of Modified Watermelon Biochar and Its Adsorption Properties for Pb(â ¡)].

In this study, watermelon rind was used as a raw material to modify watermelon rind biochar (MBC) with ammonium sulphate[(NH4)2S] for adsorption of Pb(Ⅱ) ions. The effects of solution pH, adsorption time, adsorbent addition amount, initial mass concentration of Pb(Ⅱ) ions, and ionic strength on the adsorption of Pb(Ⅱ) ions were investigated. The results show that the saturated adsorption time was 5 h, the optimum pH of the adsorption reaction was 6, and when the initial mass concentration of Pb(Ⅱ) ions were 1000 mg·L-1, and the amount of adsorbent was 2.0 g·L-1. The maximum adsorption amount of MBC to Pb(Ⅱ) ions can reach 97.63 mg·g-1, which is significantly higher than unmodified watermelon husk biochar (BC). The adsorption of Pb(Ⅱ) ions by modified watermelon biochar was in accordance with the Langmuir isotherm adsorption model and the pseudo second-order kinetic model, which proves that adsorption is dominated by monolayer chemical adsorption. The desorption of MBC after adsorption of Pb(Ⅱ) ions was carried out using a sodium hydroxide solution to study the reusability of MBC, and the adsorption amount was still 64.74 mg·g-1 in the sixth cycle. Characterization and analysis of adsorbents by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, nitrogen adsorption, scanning electron microscopy-energy spectroscopy, zeta potential analysis, and X-ray diffraction (XRD) were carried out, which showed that the adsorption mechanism is mainly that MBC oxygen- and MBC sulfur-containing groups adsorb Pb(Ⅱ) through complexation and precipitation. Therefore, ammonium sulfide modified watermelon rind biochar can be used as a highly efficient lead adsorbent.

Ligustrazine reverts anthracycline chemotherapy resistance of human breast cancer by inhibiting JAK2/STAT3 signaling and decreasing fibrinogen gamma chain (FGG) expression.

Chemotherapy resistance is a major challenge for breast cancer treatment. It is necessary to elucidate the mechanisms of anthracycline resistance to develop new chemosensitizers for breast cancer. In this study, we explored the effects of ligustrazine (TMP) on reverting anthracycline resistance of breast cancer cells, as well as its related mechanisms. Clinical significance of fibrinogen gamma chain (FGG) expression was also analyzed in breast cancer tissues. We provided evidence that breast tumor cell derived FGG participated in anthracycline chemoresistance of breast cancer. Further, TMP reverted epirubicin resistance by inhibiting JAK2/STAT3 signaling and decreasing FGG expression. Meanwhile, the elimination of cancer stem cell was observed in TMP treated chemoresistant breast cancer cells. Clinical analysis demonstrated that patients with FGG expressing breast cancer showed a dramatically low response to anthracycline-based chemotherapy and poor survival. Our data collectively indicated that FGG was an independent detrimental factor for anthracycline based chemotherapy for breast cancer patients. TMP was a novel chemosensitizer for FGG-induced anthracycline chemoresistance in breast cancer treatment.

Annexin A13 predicts poor prognosis for lung adenocarcinoma patients and accelerates the proliferation and migration of lung adenocarcinoma cells by modulating epithelial-mesenchymal transition.

This study aimed to investigate the role of ANXA13 in lung adenocarcinoma (LUAD) growth, migration, and the underlying mechanisms. Firstly, in the TCGA dataset for LUAD, ANXA13 is found to be highly expressed in patients with LUAD and high expression of ANXA13 predicted poor outcomes in LUAD patients. Consistently, the data of qRT-PCR showed that the expression of ANXA13 was higher in LUAD cell lines (Calu-3, LTEP-a-2, and NCI-H1395) than that in normal lung cell line BEAS2B. Then, we performed gain- and loss of function of ANXA13 in NCI-H1395 and Calu-3 cells, respectively. The results displayed that deficiency of ANXA13 suppresses cell proliferation, invasion, and migration in Calu-3 cells and overexpression of ANXA13 augments cell proliferation, invasion, and migration in NCI-H1395 cells. Finally, it was found that silencing of ANXA13 obviously raised the protein expression levels of E-cadherin and reduced the protein levels of N-cadherin, Vimentin, and Snail in Calu-3 cells whereas overexpression of ANXA13 obviously receded the protein expression levels of E-cadherin and enhanced the protein levels of N-cadherin, Vimentin, and Snail in NCI-H1395 cells. This study analyzed the biological effects of ANXA13 in LUAD cells, indicating that ANXA13 could regard as a therapeutic target for LUAD.

Microwave ablation plus chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a multicenter, randomized, controlled, phase III clinical trial.

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

A novel sewage sludge biochar and ferrate synergetic conditioning for enhancing sludge dewaterability.

A great prospect of sewage sludge self-recycling as a conditioner supports the research. A synergetic conditioning effect and mechanism were reflected after the synergistic conditioning experiment, and the corresponding separated experiment of biochar, K2FeO4 or acid treatment on WAS. All of the biochar, K2FeO4 and acid treatment could reduce the water content of sludge cake. Biochar had good effect on WAS settleability, although the influence of the biochar dosage was weak. Similar to K2FeO4, acid treatment also could reinforce the disintegration degree effectively, but it deteriorated the filter property of WAS. In the situation of synergistic condition, owing to the strong oxidation of K2FeO4, most of the sludge flocs was disintegrated, thus the settleability and filter property of WAS were still bad, even the biochar worked as a skeleton builder. It is encouraging to find that, even without acid treatment, there is a great decline of water content of sludge cake in the situation of synergistic condition.

Local Thermal Ablation with Continuous EGFR Tyrosine Kinase Inhibitors for EGFR-Mutant Non-small Cell Lung Cancers that Developed Extra-Central Nervous System (CNS) Oligoprogressive Disease.

BACKGROUND: Most epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs) experience oligoprogressive disease. Local ablation for isolated resistant sites continued with the original EGFR-TKI showed good efficacy in these patients. We conducted this multicenter retrospective study to investigate the potential benefit of thermal ablation in NSCLC patients that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment. METHODS: A total of 71 EGFR-mutant patients treated with EGFR-TKIs were identified. Progression-free survival 1 (PFS1) was calculated from the initiation of TKI treatment to first progression. Patients with metastatic sites ≤ 3 in less than 3 extra-CNS organs suitable for local ablation therapy received either radiofrequency ablation or microwave ablation to these sites and continued on the original TKIs. PFS2 was defined from the first progression to second progression after ablation. RESULTS: The median PFS1 for all patients was 11.8 months. Eighty extra-CNS oligoprogressive lesions in 71 patients were ablated. Thirty-six of 71 patients progressed after thermal ablation and 31 of whom died during the study period. The median PFS2 after thermal ablation was 10.0 months, and the median overall survival was 26.4 months. PFS1 and PFS2 were highly correlated with OS, whereas PFS1 was not correlated with PFS2. The numbers of oligoprogressive lesions were significantly and independently associated with PFS2. CONCLUSION: Local thermal ablation for the oligoprogressive lesions with continuous EGFR-TKI treatment is associated with additional 10 months of disease control and should be recommended in TKI acquired resistant-NSCLC patients.

PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer.

Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the PIK3CA gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with PIK3A mutation showed worse response to first-line chemotherapy than those without PIK3CA mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5+ CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore, PIK3CA mutation/LGR5+ expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA mutation/LGR5+ expression was a potential biomarker for monitoring chemotherapy resistance in CRC.

Metaplastic breast carcinoma composed of epithelial-myoepithelial carcinoma and squamous cell carcinoma: A case report.

RATIONALE: Metaplastic breast carcinomas are a group of breast malignancies with varying histomorphological characteristics and prognoses. The tumor composed of epithelial -myoepithelial carcinoma and squamous cell carcinoma was not reported previously. PATIENT CONCERNS: An 81-year-old woman presented with a palpable nodule in the left breast for 4 days. The ultrasonography showed multinodular growth and focally indistinct borders. Owing to her advanced age and possible early clinical staging, primary tumor resection was performed. One year later, a small and slow growing subcutaneous nodule was found under the incision of the left breast. Ultrasonography revealed an irregular, cystic and solid, hypoechoic mass with circumscribed borders. DIAGNOSES: Microscopic examination of the primary tumor revealed epithelial -myoepithelial carcinoma and squamous cell carcinoma. The former had a variety of architecture patterns, including nests, lobulations, papillary and tubular structures, and the latter showed varying morphological features, from squamous pearls to spindle cells. The recurrent tumor showed only epithelial -myoepithelial carcinoma with more aggressively malignant features than those seen in the primary tumor. INTERVENTIONS: An extensive resection of the left breast mass was performed for the recurrent tumor. The patient did not receive any adjuvant chemotherapy or radiation therapy because of the patient's advanced age. OUTCOMES: The patient has been followed up for 1.5 years after second surgery without evidence of tumor recurrence and metastasis. LESSONS: Wide local excision with adequate margins is recommended for elderly patients with metaplastic breast carcinoma composed of epithelial -myoepithelial carcinoma and squamous cell carcinoma.

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.

Associations between body mass index and the risk of mortality from lung cancer: A dose-response PRISMA-compliant meta-analysis of prospective cohort studies.

BACKGROUND: Whether body mass index (BMI) is associated with the risk of mortality from lung cancer (LC) is controversial, and the shape of dose-response relationship on this topic is not well-established. Thus, a dose-response meta-analysis was performed to clarify this association. METHODS: A search of PubMed and EMBASE was conducted, and 2-stage random-effect dose-response model was used to yield summary relative risks and its shape. RESULTS: Fifteen prospective cohort studies were eligible for inclusion criteria. The combined relative risks per 5 kg/m in BMI for risk of LC mortality is 0.94 (95% confidence interval] 0.92-0.96), and nonlinear association was found (Pnonlinearity < .0001), which indicated that compared with higher BMI, lower BMI showed higher LC mortality risk. Subgroup analyses revealed that this obesity paradox remained regardless of number of cases, follow-up duration, and study location, but this relationship was not observed among nonsmokers. CONCLUSION: A nonlinear association between BMI and the risk of LC mortality was found, and higher BMI participants have a lower risk of LC death than slim people.

Short-Term Outcomes and Safety of Computed Tomography-Guided Percutaneous Microwave Ablation of Solitary Adrenal Metastasis from Lung Cancer: A Multi-Center Retrospective Study.

OBJECTIVE: To retrospectively evaluate the short-term outcomes and safety of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of solitary adrenal metastasis from lung cancer. MATERIALS AND METHODS: From May 2010 to April 2014, 31 patients with unilateral adrenal metastasis from lung cancer who were treated with CT-guided percutaneous MWA were enrolled. This study was conducted with approval from local Institutional Review Board. Clinical outcomes and complications of MWA were assessed. RESULTS: Their tumors ranged from 1.5 to 5.4 cm in diameter. After a median follow-up period of 11.1 months, primary efficacy rate was 90.3% (28/31). Local tumor progression was detected in 7 (22.6%) of 31 cases. Their median overall survival time was 12 months. The 1-year overall survival rate was 44.3%. Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4%. Of 36 MWA sessions, two (5.6%) had major complications (hypertensive crisis). CONCLUSION: CT-guided percutaneous MWA may be fairly safe and effective for treating solitary adrenal metastasis from lung cancer.

Significant partial response of metastatic intra-abdominal and pelvic round cell liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib: A case report.

INTRODUCTION: Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating advanced myxoid/round cell liposarcoma, with relatively serious side effects. CASE PRESENTATION: We herein present a 68-year-old Chinese woman initially diagnosed with advanced multiple intra-abdominal and pelvic round cell liposarcoma.She refused to receive cytotoxic chemotherapy and received apatinib as the first-line therapy, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. No serious drug-related side effects were observed. CONCLUSION: Our findings indicate that some cases of liposarcoma may be responsive to antiangiogenic agent apatinib. Randomized clinical studies are needed to further confirm the efficacy and safety of apatinib in the clinical treatment of liposarcoma.

Local microwave ablation with continued EGFR tyrosine kinase inhibitor as a treatment strategy in advanced non-small cell lung cancers that developed extra-central nervous system oligoprogressive disease during EGFR tyrosine kinase inhibitor treatment: A pilot study.

The non-small cell lung cancer (NSCLC) patients that experienced good clinical response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) will ultimately develop acquired resistance. This retrospective study was performed to explore the potential survival benefit of microwave ablation (MWA) therapy in epidermal growth factor receptor (EGFR)-mutant NSCLC that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment.We retrospectively analyzed 54 NSCLC patients with EGFR mutations who showed a clinical benefit from initial EGFR-TKI therapy and developed extra-CNS oligoprogressive disease at our institutions. Twenty eight patients received MWA as a local therapy for the metastatic sites and continued on the same TKIs (MWA group). The following 26 patients received systemic chemotherapy after progression (chemotherapy group). The progression-free survival (PFS1) was calculated from initiation of targeted therapy to first progression. Progression-free survival (PFS2) was defined from first progression to second progression after MWA or chemotherapy. Overall survival (OS) was calculated from the time of diagnosis to the date of last follow-up or death.The median PFS1 for both groups was similar (median 12.6 vs. 12.9 months, HR 0.63). However, the MWA group patients had a significantly longer PFS2 (median 8.8 vs. 5.8 months, hazards ratio [HR] 0.357) and better OS (median 27.7 vs. 20.0, HR 0.238) in comparison with chemotherapy group. Multivariate analysis and the internal validation identified MWA as the main favorable prognostic factor for PFS2 and OS. In the MWA group, the median PFS2 for complete ablation was significantly longer than that for incomplete ablation (11 vs. 4.2 months, HR 0.29, P < 0.05).MWA with continued EGFR inhibition might be associated with favorable progression-free survival (PFS) and OS in patients with extra-CNS oligometastatic disease. MWA as a local therapy for extra-CNS oligometastatic disease should be considered for NSCLC with acquired resistance to EGFR-TKIs.

[A multicenter, randomized, controlled, phase â ¢ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer].

OBJECTIVE: To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application. METHODS: According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle. RESULTS: The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 µg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 µg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581). CONCLUSIONS: In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 µg/kg/d, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Association of androgen receptor exon 1 CAG repeat length with risk of hepatocellular carcinoma: a case-control study.

Epidemiologic and biological data suggest a role for androgens and perhaps their receptor in hepatocellular carcinoma (HCC) development. However, few studies evaluated an association between HCC risk and androgen receptor (AR) cytosine, adenine, guanine (CAG) repeat length. To examine whether the relationship between the AR CAG repeats and HCC risk was also evident in Chinese, we conducted this large population-based, case-control study of 2,000 pathologically confirmed HCC patients and 2,000 frequency-matched controls. Two different approaches for AR CAG repeat length (analyses with continuous and categorized polymorphism variables) were conducted in the statistical analyses. For AR CAG longer allele (CAG_L), we found that subjects with longer AR CAG_L repeats had a decreased risk of developing HCC (OR = 0.87 for per CAG_A increase, 95 % CI 0.82-0.96, P = 5.33 × 10(-4)). Compared to those with the shorter (<23) CAG_L repeat length, subjects in the category of longer (≥23) CAG_L repeats had a significant 20 % decreased HCC risk (OR = 0.80, 95 % CI 0.71-0.91, P = 6.16 × 10(-4)). These findings suggest that androgen signaling underlies the development of HCC.

Nrf2 expression participates in growth and differentiation of endometrial carcinoma cells in vitro and in vivo.

The expression level of Nrf2 is increased in series of tumors and it plays a vital role in proliferation of cancer cells. However, little is known about the clinical implications and biological functions of Nrf2 in endometrial carcinoma. The aim of this study is to study whether up-regulation of Nrf2 expression can promote growth of endometrial carcinoma cells. Using immunohistochemistry, Nrf2 protein expression was analyzed in endometrial carcinoma patients. A series of assays was performed to elucidate the role of Nrf2 in growth of endometrial carcinoma. Positive rate of Nrf2 was 64.3 % (45/70) in endometrial carcinoma patients, and it was associated with FIGO stage and histological grade (P < 0.05). In addition, ectopic overexpression of Nrf2 promoted the growth of endometrial carcinoma cells in vitro and in vivo. Interestingly, Nrf2 protein translocation from cytoplasm to nucleus may influence differentiation of endometrial carcinoma cells. These results suggest that Nrf2 participates in progression of endometrial carcinoma by influencing the growth and differentiation of endometrial carcinoma cells, and it could be used as a novel and potential therapeutic target for endometrial carcinoma.