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MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional gene expression via binding to the 3'-untranslated region (3'-UTR) of targeted mRNAs. They are reported to play important roles in tumorigenesis and progression of various cancers. Among them, miR-149 was confirmed to be aberrantly regulated in various tumors. In this review, we provide a complex overview of miR-149, particularly summarize the critical roles of it in cancers and expect to lay the foundation for future works on this important microRNA.

microRNAs (miRNAs) are small noncoding RNAs that could regulate post-transcription level through binding to 3' untranslated region (3'UTR) of target messenger RNAs (mRNAs), which were reported to be related with the incidence and development of diverse neoplasms. Among them, miR-197 was confirmed to play a vital role of oncogene or anti-oncogene in different cancers via targeting key tumorigenic or tumor-suppressive genes. Additionally, miR-197 had extensively been studied in carcinogenesis progression of cancers through various mechanisms, including apoptosis, proliferation, angiogenesis, metastasis, drug resistance and tumor suppressor, and also played a role in prognosis of cancers. In this review, we summarized the roles of miR-197 in cancers and considered it as a potentially novel biomarker for different cancers, offering an alternatively secure and effective tool in molecular targeting cancer treatment.

A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment.

Liver X receptor (LXR) has been exploited widely as a drug target in breast cancer treatment, and various mechanisms underlying the effects of LXR in this area are well studied. The activated LXR plays important roles in estrogen receptor α (ERα) breast cancer cells, such as reducing cell proliferation and arresting cell cycle progression. Different LXR ligands have diverse effects on the development of breast cancer, such as the inhibitory effect of oxysterol, which can return cells to normocholesterol conditions and target other metabolic genes. Moreover, 27-hydroxycholesterol, a locally produced cholesterol metabolite, reportedly promotes the proliferation of ERα breast cancer cells in vitro and facilitates tumor metastasis with other LXR ligands. Moreover, the expression of LXR also exerts potential effects on immune surveillance, tumor immunity, and tumor microenvironment. These advances in breast cancer research indicate that LXR may be a new therapeutic target to treat the refractory or drug-resistant subtypes of breast cancer.

Previous studies concerning the association between aspirin use and breast cancer risk yielded inconsistent results. We aimed to investigate the association by meta-analysis. PubMed and EMBASE were searched for relevant studies. We calculated the summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models. Seventeen cohort studies and 15 case–control studies were included. The overall result showed that aspirin use decreased risk of breast cancer (RR, 0.90; 95% CI, 0.85–0.95). However, there was evidence of publication bias and heterogeneity and the association disappeared after correction using the trim-and-fill method. When stratified by study design, a significant benefit for aspirin users was only found in population-based and hospital-based case–control studies but not in cohort or nest case–control studies. Further subgroup analyses showed that aspirin use could decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Aspirin use may not affect overall risk of breast cancer, but decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Considering between-study significant heterogeneity and publication bias, confirmation in future studies is also essential. Cancer Epidemiol Biomarkers Prev; 24(11); 1645–55. ©2015 AACR.

Cancer stem cells (CSCs) or tumor-initiating cells (TICs), a small subset of tumor cells, are involved in tumor initiation, progression, recurrence and metastasis. In human hepatocellular carcinoma (HCC), TICs are enriched with cell surface markers and play a key role in chemotherapy resistance, tumor invasion and migration. Toll like receptor 4 (TLR4), acting as a receptor for lipopolysaccharide (LPS), has been reported to be responsible for carcinogenesis, invasion, metastasis and cancer progression. In our study, two HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasive ability of TLR4 positive HCC cells in vitro and in vivo. Stem-like features were also detected in TLR4 positive HCC cells. A total of 88 clinical samples from HCC patients were used to evaluate the association of TLR4 and stem-cell marker expression, and the relationship between TLR4 expression and clinicopathological characteristics was analyzed. The in vitro and in vivo experiments indicated that TLR4 positive HCC cells displayed significantly enhanced invasion and migration, and stem-like properties were also detected in TLR4 positive HCC cells. Clinically, TLR4 expression levels were found to be significantly higher in HCC tissues with microvascular invasion. Additionally, high expression of TLR4 in HCC tissues was strongly associated with both early recurrence and poor survivals in patients. Our results indicated that there was a relationship between TLR4 expression and CSC's features, TLR4 may act as a CSC marker, prompting tumor invasion and migration, which contributes to the poor prognosis of HCC.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expressions at posttranscriptional level. Growing evidence points to their significant role in the acquisition of drug resistance in cancers. Studies show that miRNAs are often aberrantly expressed in human cancer cells which are associated with tumorigenesis, metastasis, invasiveness, and drug resistance. Breast cancer is the leading cause of cancer-induced death in women. Over the last decades, increasing attention has been paid to the effects of miRNAs on the development of breast cancer drug resistance. Among them, miR-155 takes part in a sequence of bioprocesses that contribute to the development of such drug resistance, including repression of FOXO3a, enhancement of epithelial-to-mesenchymal transition (EMT) and mitogen-activated protein kinase (MAPK) signaling, reduction of RhoA, and affecting the length of telomeres. In this review, we discuss the role of miR-155 in the acquisition of breast cancer drug resistance. This will provide a new way in antiresistance treatment of drug-resistant breast cancer.

Metastasis is the most lethal attribute of human malignancy. High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer. Previous studies indicate that a mutation of the threonine residue at position 34 (Thr34Ala) of survivin generates a dominant-negative mutant that induces apoptosis, inhibits angiogenesis, and suppresses highly metastatic breast carcinoma in mouse models. We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis. The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages. We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A (Lip-mS), Lip-plasmid (Lip-P), or normal saline (NS). Eight days after the last dose, five randomly chosen mice from each group were sacrificed. We detected the apoptotic index, microvessel density (MVD), lymphatic microvessel density (LMVD), and the expression of VEGF-D with immunohistochemistry. After the remaining animals were sacrificed, we compared the tumor-infiltrated lymph nodes in each group. Administration of mSurvivinT34A plasmid complexed with cationic liposome (DOTAP/chol) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model. These responses were associated with tumor cell apoptosis, and angiogenesis and lymphangiogenesis inhibition. Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis, thus suppressing tumor growth and lymphatic metastasis. The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis.

Background The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-γ (IFN-γ) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. Methods We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-γ rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. Results VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-γ rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). Conclusions These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-γ.

We investigated IgA and IgG levels against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1) in serum of 223 women with breast cancer (BC) and 309 controls in Guangzhou, China. VCA IgA levels were significantly associated with an elevated risk of BC, with adjusted ORs (95%CIs) of 1.70 (1.05-2.76) (seropositivity) and 2.21 (1.11-4.40) (unit increases in OD value). This association was stronger among young, lean, and HER2+ women. The EBNA-1 IgA levels in OD value, but not seropositivity, were associated with an increased risk of BC among ER+, PR+, and HER2+ patients. None of the IgG variables was related to BC. These results suggest the EBV association with BC in an endemic area of nasopharyngeal carcinoma.

Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this cancer, but the contributions of family history of other types of cancer and its interaction with environmental factors have not been well characterized.A total of 1845 incident cases of NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for smoking, consumption of alcohol, salted fish consumption, and demographic factors.A significant association between the risk of NPC and family history of any cancers in first degree relatives was observed, and higher number of affected family member was related to a higher risk (P(trend)0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46-4.55 for all first degree relatives). The risk of NPC was also positively associated with history of head and neck cancer among parents and lung and breast cancers among siblings. The combination of family history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased the risk for NPC.These results confirm that the risk for NPC increases with family history of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction between family history of cancer, especially NPC, and consumption of salt-preserved fish in the development of NPC was also identified.

Patients with localized prostate cancer can usually achieve initial response to conventional treatment. However, most of them will inevitably progress to advanced disease stage. There is a clear need to develop innovative and effective therapeutics for prostate cancer. Mouse survivin T34A (mS-T34A) is a phosphorylation-defective Thr34 → Ala dominant negative mutant, which represents a potential promising target for cancer gene therapy. This study was designed to determine whether mS-T34A plasmid encapsuled by DOTAP-chol liposome (Lip-mS) has the anti-tumor activity against prostate cancer, if so, to further investigate the possible mechanisms. In vitro, TRAMP-C1 cells were transfected with Lip-mS and examined for apoptosis by PI staining and flow cytometric analysis. In vivo, subcutaneous prostate cancer models were established in C57BL/6 mice, which were randomly assigned into three groups to receive i.v. administrations of Lip-mS, pVITRO2-null plasmid complexed with DOTAP-chol liposome (Lip-null) or normal saline every 2 days for eight doses. Tumor volume was measured. Tumor tissues were inspected for apoptosis by TUNEL assay. Microvessel density (MVD) was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cell test was conducted to evaluate the treatment effect on angiogenesis. Administration of Lip-mS resulted in significant inhibition in the growth of mouse TRAMP-C1 tumors. The anti-tumor response was associated with increased tumor cell apoptosis and decreased microvessel density. The present study may be of importance in the exploration of the potential application of Lip-mS in the treatment of a broad spectrum of tumors.

Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827‑8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis- and/or trans‑regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.

Hepatocyte nuclear factor-1beta (HNF1β) was initially identified as a liver-specific transcription factor. It is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF1α. HNF1β plays an important role in organogenesis during embryonic stage, especially of the liver, kidney, and pancreas. Mutations in the HNF1β gene cause maturity-onset diabetes of the young type 5 (MODY5), renal cysts, genital malformations, and pancreas atrophy. Recently, it has been shown that the expression of HNF1β is associated with cancer risk in several tumors, including hepatocellular carcinoma, pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. HNF1β also regulates the expression of genes associated with stem/progenitor cells, which indicates that HNF1β may play an important role in stem cell regulation. In this review, we discuss some of the current developments about HNF1β and tumor, the relationship between HNF1β and stem/progenitor cells, and the potential pathogenesis of HNF1β in various tumors.

Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. Here we investigate the effects of two novel liver x receptor (LXR) ligands (T0901317 or GW3965) on the development of acquired resistance to an EGFR TKI gefitinib. We observed known mechanisms of acquired resistance to EGFR TKI, including the EGFR T790M mutation, MET gene amplification and loss of PTEN in the gefitinib-resistant HCC827-8-1 cells. However, we found expression of MET was lower in HCC827-8-1 cells than in HCC827 cells. T0901317 or GW3965 inhibited Akt activation and sensitized HCC827-8-1 cells to gefitinib-induced cytotoxicity. In contrast, LXR ligands alone had no significant effect on HCC827-8-1 cells. In conclusion, this combined treatment may be of interest for treatment of lung adenocarcinomas harboring EGFR mutations and acquired resistance to gefitinib.

While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.

Hepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary specification of hepatoblasts to cholangiocytes during liver development and is strongly expressed throughout adult biliary epithelium. The aim of this study was to examine the expression of HNF-1B in different pathologic subtypes of primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (ICC) and the relationship between HNF-1B expression, clinicopathological features and prognosis. We retrospectively investigated 2 cohorts of patients, including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by immunohistochemistry. We found that HNF-1B expression was associated with pathological subtype of primary tumor and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence. The HNF-1B expression was positively correlated with biliary/HPC (hepatic progenitor cell) markers expression. Further, multivariable analysis showed that HNF-1B expression was an independent prognostic factor for both overall survival and disease-free survival of HCC patients. However, no correlation between HNF-1B expression and survival was found in ICC patients. In summary, HCC with high HNF-1B expression displayed biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant cells could be bipotential cells and give rise to both hepatocytic and cholangiocytic lineages during tumorigenesis.

Background Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-α (TNF-α), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-α on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-α on acute liver injury induced by carbon tetrachloride (CCl4). Methods SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutaneously injected into the rats. Enbrel, a TNF-α inhibitor, were intraperitoneally injected at dose of 0, 0.25, 0.5, 1, 2, 4 or 8 mg/kg 15 min before the CCl4 injection. 24 h later, rats were sacrificed. Serum ALT and AST were measured with an autoanalyzer. Serum TNF-α were measured by ELISA. HE staining was used to observe the liver tissue morphology. Hepatocellular apoptosis were tested by immunochemistry and Tunnel kit. Inflammatory factors, involve IL-4, IL-6, IL-8, IL-β and IFN-γ were detected by RT-PCR. The NF-κB signal pathway and anti-apoptotic genes include Bcl-XL, FHC, XIAP and Bcl-2 were measured by western-blotting and RT-PCR. Results The change of liver function presented an obvious “V” shape in the whole process of persistently increased Enbrel. As Enbrel was increased gradually from 0 to 1 mg/kg, serum TNF-α were blocked, ALT and AST were gradually decreased as TNF-α as well as the numbers of hepatocellular apoptosis, and were declined to the minimum at 1 mg/kg Enbrel. As Enbrel was increased gradually from 1 to 8 mg/kg, ALT, AST and hepatocellular apoptosis were increased instead, and reached to the maximum at 8 mg/kg Enbrel. HE showed that the seriousness of hepatocellular steatosis was the most at 8 mg/kg Enbrel, and second at 0 mg/kg, the weakest at 1 mg/kg in the acute liver injury. Western-blotting and RT-PCR showed NF-κB, p-IκBα and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-α was blocked by increased Enbrel. Conclusion Our results suggested that TNF-α had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-κB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury. Electronic supplementary material The online version of this article (doi:10.1186/s13578-016-0074-x) contains supplementary material, which is available to authorized users.

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor, which is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. Dermatological reactions are the most common adverse events associated with gefitinib treatment; other adverse effects, including diarrhea, nausea, stomatitis and an asymptomatic elevation of liver enzymes have also been reported. The present study describes a patient with intestinal obstruction who was successfully undergoing treatment with gefitinib for primary and metastatic neoplasms. Gefitinib-induced intestinal obstruction has not been previously reported; therefore, careful monitoring of gastrointestinal symptoms should be conducted throughout the course of gefitinib-treated malignancies.

Propofol-paravertebral anesthesia (PPA) is a unique combination of paravertebral nerve blocks (PVBs) and propofol that regulates the cellular microenvironment during surgical period. Growing evidence points to its ability to attenuate perioperative immunosuppression of cancers. Abundant studies show that cancer patients who undergo perioperative PPA exhibit less recurrence as well as metastasis. Breast cancer remains a leading cause of cancer-induced death in women. Over the last decades, increasing concerns have been put on the promotional role of PPA in the prognosis of breast cancer patients. Among them, PPA participates in several bioprocesses in the development of breast cancer, including inhibiting hypoxia-inducible factor (HIF) activity, elevating serum concentration of nitric oxide index (NOx), depression of the neuroepithelial cell transforming gene 1 (NET1) signal pathway, blocking the nuclear factor kappa B (NF-κB) pathway following an decreased expression of matrix metalloproteinase (MMP), increasing NK cytotoxicity, and affecting transforming growth factor (TGF)-β-targeted ras and HER2/neu gene pathways. In this review, we discuss the effect of PPA on breast cancer metastasis and progression. This will provide an alteration pattern of surgical anesthesia technique in breast cancer patients with poor prognosis.

Breast cancer (BCa) is one of the major deadly cancers in women. However, treatment of BCa is still hindered by the acquired-drug resistance. It is increasingly reported that exosomes take part in the development, metastasis, and drug resistance of BCa. However, the specific role of exosomes in drug resistance of BCa is poorly understood. In this study, we investigate whether exosomes transmit drug resistance through delivering miR-222. We established an adriamycin-resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line (MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by fluorescence in situ hybridization (FISH). Then, FISH was combined with locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual miR-222 could be detected as bright photostable fluorescent spots and then the quantity of miR-222 per cell could be counted. Stained exosomes were taken in by the receipt cells. MCF-7/S acquired drug resistance after co-culture with exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR-222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222 inhibitors lost resistance. In conclusion, exosomes are effective in transmitting drug resistance and the delivery of miR-222 via exosomes may be a mechanism.

Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients.

Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

Strontium has been widely used in industries like electronic and pharmacy. It has a carcinogenic potential, however, and no study has been conducted to evaluate its effects on cancer risk. The aim of this study was to explore the possible association between strontium and breast cancer risk in a case-control study including 240 incident invasive breast cancer patients and 246 age-matched controls. We measured the urinary concentrations of strontium by inductively coupled plasma mass spectrometry, and conducted face-to-face interviews to obtain information on potential breast cancer risk factors. Multivariable analysis was used to estimate the association. Creatinine-adjusted levels [median (25th, 75th) μg/g] of strontium were 155.59 (99.05, 230.70) in the breast cancer patients and 119.62 (81.97, 163.76) in the controls. Women in the highest tertile of strontium showed 124% increased risk of breast cancer, when compared with those in the lowest tertile after adjustment for the potential risk factors [OR (95% CI): 2.24 (1.42-3.81)]. This association was particularly strong for HER2 positive breast cancer [OR (95% CI): 10.92 (3.53-33.77)], and only occurred among premenopausal women. These results suggest a potential role of strontium in the development of breast cancer and urge further studies on the environmental contamination and the physiological and pathological mechanisms of strontium.

Radiosensitivity of tumors is due to a complex interaction of various factors, it has been reported that survivin also acts as a constitutive and inducible radioresistance factor in a panel of tumor cells and approaches designed to inhibit survivin expression or function may lead to tumor sensitisation to chemical and physical agents. Previously, we found that the plasmid encoding the phosphorylation-defective mouse survivin threonine 34-->alanine mutant complexed to DOTAP-chol liposome (Lip-mS) can suppress murine primary breast carcinoma. However, little is known regarding the biological effect of Lip-mS combined with radiation. The present study was designed to determine whether Lip-mS could enhance the anti-tumor activity of radiation. The Lewis Lung Carcinoma (LLC) cells treated with a combination of Lip-mS and radiation displayed apparently increased apoptosis compared with those treated with Lip-mS or radiation alone. Mice bearing LLC tumors were treated with intravenous injections of Lip-mS and radiation, the combined treatment significantly reduced mean tumor volume compared with either treatment alone. Moreover, the anti-tumor effect of Lip-mS combined with radiation was greater than their additive effect when compared with the expected effect of the combined treatment. These data suggest that inhibition of survivin using a dominant-negative mutant, survivin T34A, could sensitize LLC cells to radiation efficiently and the synergistic anti-tumor activity may in part result from increasing the apoptosis of tumor cells, inhibiting tumor angiogenesis and inducing a tumor-protective immune response in the combined treatment.

Development of a tumor is a very complex process, and invasion and metastasis of malignant tumors are hallmarks and are difficult problems to overcome. The tumor microenvironment plays an important role in controlling tumor fate and autophagy induced by the tumor microenvironment is attracting more and more attention. Autophagy can be induced by several stressors in the tumor microenvironment and autophagy modifies the tumor microenvironment, too. Autophagy has dual roles in tumor growth. In this review, we discussed the interaction between autophagy and the tumor microenvironment and the paradoxical roles of autophagy on tumor growth at different stages of tumor development.