Effects of Selenium and Cadmium on Human Liver and Kidney Functions in Exposed Black Shale Areas.

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long-term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B-Se) and urine selenium (U-Se) levels were detected in these areas, measuring 416.977 µg/L and 352.690 µg/L and 104.527 µg/L and 51.820 µg/L, respectively. Additionally, the median blood Cd (B-Cd) and urine Cd (U-Cd) levels were markedly elevated at 4.821 µg/L and 3.848 µg/L and at 7.750 µg/L and 7.050 µg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 µmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 µmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

Bifidobacterium modulation of tumor immunotherapy and its mechanism.

The advent of tumor immunotherapy in patients has revolutionized the treatment of tumors and significantly improved survival rates for a wide range of tumors. However, the full therapeutic potential of immune checkpoint inhibitors (ICIs) has yet to be realized, as not all patients have a lasting survival benefit from them, and a significant proportion of patients show primary or acquired resistance to immunotherapy. Bifidobacterium is one of the most common probiotics, and its antitumor and immunomodulatory effects have been demonstrated in recent years, but its immunomodulatory effects in tumors, especially on ICIs and in combination, have not been extensively studied in clinical practice, and its effects on the immune system and the mechanisms that modulate immunotherapy are largely unknown. Therefore, this review will focus on the immunomodulatory effects of Bifidobacteria in malignancies and the possible mechanisms of action of Bifidobacteria on immunotherapy in the hope of providing a basis for further research and better application of Bifidobacteria in clinical practice.

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.

Effects of selenium supplementation on concurrent chemoradiotherapy in patients with cervical cancer: A randomized, double-blind, placebo-parallel controlled phase II clinical trial.

Objective: Selenium (Se) is an essential trace element and may affect cervical cancer occurrence and progression. The association between selenium supplementation and acute toxic reactions and clinical outcomes in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy remains unclear. The aim of this study was to determine the safety profile of add-on Se yeast and assess the potential of Se to ameliorate the hematologic toxicity of concurrent chemoradiotherapy in patients with cervical cancer. Methods: Patients with Federation International of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer who met all inclusion criteria were randomly assigned to either the experimental group or the control group. The experimental group received Se yeast tablets (100 µg Se, twice daily), while the control group received placebos (twice daily) for 5 weeks in total. All patients in both groups received standard treatment, including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy. Measures included the incidence of myelosuppression, impairment of liver and kidney function, objective response rate (ORR), and blood Se concentrations before, during and after the treatment of the two groups. Results: A total of 104 eligible patients were enrolled in the experimental group (n = 50) or the control group (n = 54). The ORR in the experimental group and control group were 96 and 94%, respectively (p = 0.47). The baseline levels of blood Se before treatment in the experimental and control groups were similar (58.34 ± 17.63 µg/L and 60.21 ± 18.42 µg/L, p = 0.60), but the concentrations became significantly different after course completion between the two groups (76.16 ± 24.47 µg/L and 57.48 ± 14.92 µg/L, respectively, p < 0.01). Se dramatically decreased the incidence of grade 3 myelosuppression (48% vs. 63%, p = 0.034) compared to the control group. In the subgroup of patients with moderately well-differentiated cervical cancer, the incidence of thrombocytopenia induced by concurrent chemoradiotherapy was lower in the experimental group than in the control group (53.8% vs. 78.9%, p < 0.01). However, no difference was observed in liver and kidney injuries between the two groups. Conclusion: Supplementation with Se effectively increased blood Se levels in Se-inadequate cervical cancer patients. As an add-on to standard treatment, Se-yeast significantly decreased the hematologic toxicity of concurrent chemoradiotherapy.

Immunohistochemical characteristics of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case report and review.

BACKGROUND: Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is a rare nasopharyngeal malignant tumor that is easy to misdiagnose. Immunohistochemistry plays an indispensable role in distinguishing TL-LGNPPA from other malignancies. However, there is no article to summarize the immunohistochemical characteristics of TL-LGNPPA. Herein, we report a case of TL-LGNPPA and present the immunohistochemical results reported in the Chinese literature. METHODS: An electronic search of the CNKI (China National Knowledge Infrastructure) database was performed. From our literature survey, 53 cases of TL-LGNPPA (including the case described in this report) have been identified in China. We summarize the Chinese literature's clinical characteristics, immunohistochemical results, treatments, and prognosis of 53 cases. RESULTS: Based on our literature survey, 53 cases of TL-LGNPPA (including the case described in this report) have been reported in China. We found TL-LGNPPA and papillary thyroid carcinoma were positive for TTF-1 and CK19. TL-LGNPPA was negative for TG and PAX-8, whereas papillary thyroid carcinoma was positive for TG and PAX-8. However, negative expression of TTF-1 and positive expression of TG were also found in some TL-LGNPPA cases. Our literature survey found that all TL-LGNPPA cases were negative for PAX-8.Therefore, we suggest that simultaneous immunohistochemical determination of TTF-1 and CK19, as well as TG and PAX-8, can increase the diagnostic accuracy of TL-LGNPPA. CONCLUSION: The 4th edition of the World Health Organization Classification of Head and Neck Tumors (WHO-HNT) indicates that NPPA with positive expression of cytokeratin 19 (CK19) and TTF-1 and negative expression of TG is called TL-LGNPPA.

Anticancer and antibacterial flavonoids from the callus of Ampelopsis grossedentata; a new weapon to mitigate the proliferation of cancer cells and bacteria.

A new flavonoid angelioue (1) together with five known compounds cuminatanol (2), myricetin (3), epigallocatechin (4), taxifolin (5) and dihydromyricetin (6) was isolated from the callus extract of Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang and the structures were elucidated based on their detailed spectroscopic data. Among the compounds, the new compound angelioue (1) displayed significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with the MIC value of 6.68 µg mL-1 and MBC value of 53.42 µg mL-1; in contrast the other compounds showed moderate to no antibacterial activity. In addition, known dihydromyricetin (6) exhibited potent cytotoxic activities against mouse breast cancer cells (4T1), human lung adenocarcinoma (A549) and human non-small cell lung cancer (NCI-H1975) tumor cell lines with GI50 values of 17.47, 18.91 and 20.50 µM mL-1, respectively. The compounds 1-5 exhibited low micro-molar inhibitory activities. Moreover, the structure-activity relationships of the most active compounds for antibacterial and cytotoxic activities are discussed. The present findings clearly suggest that the A. grossedentata callus is a good source of bioactive compounds.

Se-Methylselenocysteine Alleviates Liver Injury in Diethylnitrosamine (DEN)-Induced Hepatocellular Carcinoma Rat Model by Reducing Liver Enzymes, Inhibiting Angiogenesis, and Suppressing Nitric Oxide (NO)/Nitric Oxide Synthase (NOS) Signaling Pathway.

BACKGROUND Hepatocellular carcinoma is the third leading cause of cancer-associated mortality. This study aimed to investigate the effects of se-methylselenocysteine (MSC) on oncogenesis of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. MATERIAL AND METHODS A hepatocellular carcinoma rat model was established by administering DEN. Rat models were divided into Model (0.1 mg/kg MSC), Model+0.3 mg/kg MSC, Model+1 mg/kg MSC, and Model+3 mg/kg MSC groups. A Normal control group consisted of mice not administered MSC. Hematoxylin and eosin staining was used to determine liver injury. Immunohistochemical analysis was conducted to identify CD34 and vascular endothelial growth factor (VEGF) expression. VEGF gene transcription was detected with RT-PCR. Biochemical analyses were performed to determine alanine aminotransferase, aspartate aminotransferase, total bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and albumin levels in serum, and nitric oxide (NO)/nitric oxide synthase (NOS) levels in liver tissues. Transmission electron microscopy was used to observe the ultra-microstructures of hepatocytes. RESULTS MSC treatment markedly alleviated liver injury and nuclear lesions in the treatment groups compared to the Model group. MSC treatment significantly improved liver functions in the treatment groups compared to the Model group (P<0.05). MSC treatment significantly decreased CD34 expression and NO and NOS levels in liver tissues and suppressed VEGF expression compared to the Model group (all P<0.05). CONCLUSIONS MSC administration alleviated liver injury in a DEN-induced hepatocellular carcinoma rat model through reducing liver enzymes, inhibiting angiogenesis, and suppressing the NO/NOS signaling pathway.

Zoledronic acid re­sensitises gefitinib­resistant lung cancer cells by inhibiting the JAK/STAT3 signalling pathway and reversing epithelial­mesenchymal transition.

Studies have shown that suppression of both the JAK/STAT3 pathway and epithelial­mesenchymal transition (EMT) may overturn the resistance of non­small cell lung cancer (NSCLC) cells to gefitinib. Zoledronic acid (ZA) injection is used to treat and prevent multiple forms of osteoporosis, hypercalcemia and bone metastasis­related complications of malignancy. Clinical research has shown that ZA may exert antitumour effects and delay the progression of NSCLC. In the present study, we investigated whether ZA combined with gefitinib could re­sensitise NSCLC cells to gefitinib in vitro and in vivo through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The results revealed that ZA potently increased the sensitivity of gefitinib­resistant lung cancer cells to gefitinib. ZA decreased activation of JAK/STAT3 signalling and reversed EMT in the H1975 and HCC827GR cell lines. Furthermore, addition of IL­6 to ZA­pretreated gefitinib­resistant cell lines abrogated the effect of ZA and restored the cellular resistance to tyrosine kinase inhibitors. Finally, ZA­based combinatorial therapy effectively inhibited the growth of xenografts derived from gefitinib­resistant cancer cells, which was correlated with the inhibition of the JAK/STAT3 signalling pathway and EMT reversal. In conclusion, ZA re­sensitised gefitinib­resistant lung cancer cells through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The combination of ZA and gefitinib may be a promising therapeutic strategy to reverse gefitinib resistance and prolong the survival of patients with NSCLC.

[miR-520a-3p regulates the signaling pathway of cytokine secretion in cervical cancer].

OBJECTIVE: To investigate the molecular mechanism of miR-520a-3p regulating the secretion of cytokines in cervical cancer. METHODS: The matching between miR-520a-3p and the NF-κB complex subunit RELA was analyzed by TargetScanHuman, and then the luciferase reporting system was used to detect whether miR-520a-3p targeted the NF-κB complex subunit RELA. After cervical cancer HELA cells stimulated by LPS, in the overexpression group or the knockout group, miR-520a-3p mimics or inhibitor were mixed with transfection reagent and dripped into HELA cells. The expression levels of colony stimulating factor (GCSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 2 (IL-2), interleukin 3 (IL-3), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 19 (IL-9), interleukin 10 (IL-10), interleukin 12 p40 (IL-12 p40), interleukin 12 p70 (IL-12 p70), interleukin 13 (IL-13), interleukin 17 (IL-17), interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-5 (MCP-5), small inducible cytokine A5 (RANTES), tumor necrosis factor-alpha (TNFα) were detected by enzyme-linked immunosorbent assay in both the overexpression group and the knockout group. Each experiment was repeated three times. RESULTS: miR-520a-3p targeted the 3'UTR of RELA. After activation of the NF-κB signaling pathway by lipopolysaccharide (LPS), the protein expression levels of cytokines GCSF, GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-17, IFN-γ, MCP-1, MCP-5, RANTES, TNFα secreted by HELA cells of cervical cancer were increased significantly (P＜0.05). In the overexpression group, the protein expression level of RELA of NF-κB complex subunit was decreased, and the protein expression level of the above-mentioned cytokines secreted by HELA cells of cervical cancer were decreased (P＜0.05). In the knockdown group, the protein expression level of RELA, a subunit of NF-κB complex, and the protein expression level of the above-mentioned cytokines secreted by HELA cells of cervical cancer were increased (P＜0.05). CONCLUSION: miR-520a-3p inhibits cytokine secretion in HELA cells of cervical cancer by targeting RELA, a key molecule in the NF-κB signaling pathway.

Enzyme-powered Janus platelet cell robots for active and targeted drug delivery.

Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.

Sodium Selenite Accentuates the Therapeutic Effect of Adriamycin Prodrug (PADM) against Gastric Cancer.

Selenium has remained a controversial character in cancer research. While its antitumor effects have been widely demonstrated, further evidence is required to establish it as a robust treatment regime. Sodium selenite (SS), an inorganic selenium, reportedly affected the proliferation and redifferentiation of gastric cancer cells, but whether it could act as a complement to conventional chemotherapeutic drugs for combination therapy is uncertain. Herein, SGC-7901 and MGC-803 gastric cancer cells were treated with PADM (Ac-Phe-Lys-PABC-ADM), a prodrug of doxorubicin/adriamycin (ADM), and the combined antitumor effects of the two drugs were evaluated. Characterization after treatment revealed that although PADM exhibited antitumor effects individually by inhibiting the proliferation and migration of gastric cancer cells and inducing apoptosis, the addition of SS significantly amplified these effects. Furthermore, gastric cancer cell apoptosis triggered by the combined treatment of SS and PADM may involve the participation of mitochondrial apoptosis, as evidenced by the changes in mitochondrial morphology and occurrence of mitochondrial fission. Collectively, SS could be a strong complementary drug that accentuates the therapeutic potential of PADM in gastric cancer treatment and management, and its significance could contribute to unique and innovative anticancer strategies.

Combination of Sodium Selenite and Doxorubicin Prodrug Ac-Phe-Lys-PABC-ADM Affects Gastric Cancer Cell Apoptosis in Xenografted Mice.

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

Serum Selenium Levels and Cervical Cancer: Systematic Review and Meta-Analysis.

Several studies have investigated the relationship between serum Se concentration and cervical cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum selenium levels and cervical cancer. Twelve studies investigating the association by univariate analysis and five studies by multivariate analysis were identified after a systematic search of PubMed, Wanfang, CNKI, and SinoMed databases. Standard mean differences (SMD) or odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. In univariate analysis, serum selenium levels in cervical cancer cases were significantly lower than in controls (SMD = -4.86, 95% CI -6.03-3.69). Subgroup analysis showed consistent results. In multivariate analysis, serum selenium levels in cervical cancer cases were also significantly lower than in controls (OR = 0.55, 95% CI 0.42-0.73). After treatment, the serum selenium levels increased significantly (SMD = 2.59, 95% CI 0.50-4.69). In conclusion, high serum selenium levels were associated with cervical cancer, and selenium exposure might be a protective factor for cervical cancer.

Angelicin inhibits human lung carcinoma A549 cell growth and migration through regulating JNK and ERK pathways.

Angelicin is a member of a well-known class of chemical photosensitizes that have anticancer proper-ties in several cancer cell lines. However, the effects and the potential underlying mechanisms of angelicin action on human lung cancer cells remain unclear. Here, we report that angelicin has an essential role in inhibiting human lung carcinoma growth and metastasis. We found that angelicin markedly induced cell apoptosis and arrested the cell cycle in vitro. Angelicin also inhibited the migration of non-small cell lung cancer (NSCLC) A549 cells in a Transwell assay in a dose-dependent manner. In addition, after angelicin treatment, the expression levels of Bax, cleaved caspase-3 and cleaved caspase-9 were increased, and Bcl-2 expression was decreased. Moreover, our results indicate that angelicin inhibits NSCLC growth not only by downregulating cyclin B1, cyclin E1 and Cdc2, which are related to the cell cycle, but also by reducing MMP2 and MMP9 and increasing E-cadherin expression levels. Furthermore, extracellular signal-regulated kinase (ERK)1/2 and c-Jun NH2-terminal protein kinase (JNK)1/2 phosphorylation increased in parallel with the angelicin treatments. The inhibition of ERK1/2 and JNK1/2 by specific inhibitors significantly abrogated angelicin-induced cell apoptosis, cell cycle arrest and migration inhibition. We established in vivo A549 cell transplant and metastasis models and found that angelicin exerted a significant inhibitory effect on A549 cell growth and lung metastasis. Overall, our results suggested that angelicin is able to inhibit NSCLC A549 cell growth and metastasis by targeting ERK and JNK signaling, which demonstrates potential for NSCLC therapy.

Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations.

Non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations and bone metastases are often concurrently administered tyrosine kinase inhibitors (TKIs) and bisphosphonates. Yet, the effects and mechanisms of these agents are unclear. In the present study, we aimed to ascertain whether zoledronic acid (ZA) increases the antitumor effects of gefitinib treatment on NSCLC with EGFR mutations and the related mechanisms of action. The effects of ZA and gefitinib on NSCLC tumor cells with EGFR mutations (HCC827, HCC827 GR and H1975) in regards to proliferation, apoptosis, cell cycle and signaling pathways were detected. ZA increased the antitumor effects of gefitinib on NSCLC with EGFR activating mutations and TKI resistance in vitro. Gefitinib caused cell cycle arrest in the G0/G1 phase, ZA induced S phase accumulation and the effect of the combined treatment was neutralization. Combined treatment obviously inhibited STAT3 and/or p­STAT3 protein expression compared with treatment with each single drug in vitro and in vivo, and it also significantly inhibited TKI resistance NSCLC tumor growth in vivo. In conclusion, ZA increased the antitumor effects of gefitinib on NSCLC with EGFR activating mutations and TKI resistance by regulating the cell cycle, inducing caspase-3 expression and inhibiting STAT3 expression.

Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study.

BACKGROUND: Bisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations. METHODS: Between January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed. RESULTS: Among the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798). CONCLUSIONS: Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.

Expression of activated signal transducer and activator of transcription-3 as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma.

BACKGROUND: Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor constitutively active and aberrantly expressed in various types of malignancies, and the expression of p-STAT3 has been recognized as a predictor of poor survival. It remains unclear how variations in p-STAT3 expression influence clinical outcomes in esophageal squamous cell carcinoma (ESCC). METHODS: Between 1 January 2008 and 1 November 2013, 153 advanced esophageal squamous cell carcinoma patients (stage IV) from two cancer centers in West China were treated with paclitaxel and cisplatin. We retrospectively analyzed the clinical outcomes of patients with ESCC and examined the correlation between p-STAT3 levels and clinical outcomes in esophageal cancer patients. RESULTS: Among the 153 patients, positive p-STAT3 expression was observed in 73 of 153 (47.7 %) cases. The median PFS for patients with positive expression of p-STAT3 and negative expression of p-STAT3 was 5.0 months and 6.9 months, respectively (P < 0.001). The median overall survival was significantly higher in patients with p-STAT3 negative tumors than in those with p-STAT3 positive tumors (9.9 vs 8.9 months, P = 0.026). Kaplan-Meier survival analysis showed that p-STAT3 expression was statistically indicative of a poor prognosis for progression-free survival. CONCLUSIONS: These data showed that p-STAT3 expression was significantly associated with poor prognosis in patients with esophageal cancer and could be used as a predictive and prognostic marker in esophageal cancer.

Carcinoma showing thymus-like differentiation of the thyroid (CASTLE).

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, probably arising from ectopic thymus or branchial pouch remnants. The tumor was first reported by Miyauchi et al. [1].The clinical and pathological features of this tumor were classified by Chan et al. [2] into 4 groups: ectopic hamartomatous thymoma, ectopic cervical thymoma, spindle ephithelial tumor with thymic-like differentiation (SETTLE), and carcinoma showing thymus-like differentiation (CASTLE). Recently, CASTLE has been designated as an independent clinicopathologic entity of thyroid tumors in the most recent edition of the World Health Organization classification of tumors of endocrine organs[3].To our knowledge, less than 100 cases of CASTLE have been reported in the literature, 45 cases of which (including one of the authors' patient) have been identified in China. We report a new case of this entity and suggest recommendations for diagnosis.