IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.

Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

[Induction cell damage and change of nuclear factor-kappa B expression by bromoxynil in SH-SY5Y cells].

OBJECTIVE: To investigate the cytotoxicity of bromoxynil on SH-SY5Y cells and its effect on the expression of nuclear factor-kappa B (NF-κB) and I kappa B alpha (IκBα) in SH-SY5Y cells. METHODS: SH-SY5Y cells were exposed to bromoxynil (10, 50, or 100 µmol/L) for 24 and 48 h, and other SH-SY5Y cells, which were used as a control, were exposed only to dimethyl sulfoxide. After 24 and 48 h of exposure, the morphological changes of these cells were observed under an inverted microscope, and the cytotoxicity of bromoxynil was measured by MTT assay. The cellular proliferation was examined by cell counting after 12, 24, 48, 72, and 96 h of exposure. After 24 h of exposure, the expression of NF-κB was evaluated by Western blot and immunocytochemistry, and the expression of IκBα was evaluated by Western blot. RESULTS: The cellular proliferation inhibition rates (CPIRs) of 50 and 100 µmol/L groups were significantly higher than that of the control group after 24 and 48 h of exposure (P < 0.05); the CPIR was significantly higher after 48 h than after 24 h in the two groups (P < 0.05). The growth curve revealed that these groups began to show differences in cell count at the 24th of exposure and that the differences were even more marked as the exposure went on (F = 17.15, P < 0.05). The control group had a significantly increased cell count at the 48th, 72nd, and 96th h of exposure (P < 0.05); the 10 and 50 µmol/L groups had a significantly increased cell count at the 72nd and 96th h of exposure (P < 0.05); the 100 µmol/L group showed no significant change in cell count during 96h of exposure. The 50 and 100 µmol/L groups hada significantly longer cell doubling time than the control group (P < 0.05). The immunocytochemistry showed that as the dose of bromoxynil increased, the brownish yellow particles in the cytoplasm and nuclei became darker, the expression of NF-κB was upregulated, and the nuclear translocation of NF-κB was increased. The Western blot showed that the 100 µmol/L group had significantly higher expression of NF-κB in the nuclei than the control group (P < 0.05) and that the 50 and 100 µmol/L groups had significantly lower expression of IκBα in total proteins than the control group (P < 0.05). CONCLUSION: Bromoxynil can inhibit the proliferation of SH-SY5Y cells under this experimental condition, which may be related to activation of NF-κB.

Mn(II)-based porous metal-organic framework showing metamagnetic properties and high hydrogen adsorption at low pressure.

A Mn(II)-based homometallic porous metal-organic framework, Mn(5)(btac)(4)(µ(3)-OH)(2)(EtOH)(2)·DMF·3EtOH·3H(2)O (1, btac = benzotriazole-5-carboxylate), has been solvothermally synthesized and structurally characterized by elemental analysis, thermogravimetric analysis, and X-ray crystallographic study. 1 is a 3D neutral framework featuring 1D porous channels constructed by {Mn-OH-Mn}(n) chains and btac linkers. Magnetic studies show that 1 is a 3D metamagnet containing 1D {Mn-OH-Mn}(n) ferrimagnetic chains. High-pressure H(2) adsorption measurement at 77 K reveals that activated 1 can absorb 0.99 wt % H(2) at 0.5 atm and reaches a maximum of 1.03 wt % at 5.5 atm. The steep H(2) absorption at lower pressure (98.2% of the storage capacity at 0.5 atm) is higher than the corresponding values of some MOFs (MIL-100 (16.1%), MOF-177 (57.1%), and MOF-5 (22.2%)). Furthermore, activated 1 can adsorb CO(2) at room temperature and 275 K. The adsorption enthalpy is 22.0 kJ mol(-1), which reveals the high binding ability for CO(2). Detailed gas sorption implies that the exposed Mn(II) coordination sites in the activated 1 play an important role to improve its adsorption capacities.

[Study on mechanism of trimethyltin chloride-induced apoptosis in PC12 cells].

OBJECTIVE: To investigate the effects of trimethyltin chloride (TMT) on proliferation, apoptosis, oxidative damage, and NF-κB expression in PC12 cells in vitro. METHODS: PC12 cells were treated with 0, 0.3125, 0.6250, 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 and 48 h, and MTT assay was used to evaluate cell viability. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 and 24 h, and flow cytometry was used to measure the apoptotic rates of cells. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 6 h, and the reactive oxygen species (ROS) and glutathione (GSH) levels were measured. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 h, and Western blot was used to measure NF-κB levels. RESULTS: Compared with solvent controls, the PC12 cells treated with 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 h showed significantly decreased cell viability (P < 0.05); the PC12 cells treated with 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 48 h showed significantly decreased cell viability (P < 0.05). The PC12 cells treated with 1.2500, 2.5000, 5.0000, and 10.0000 µmol/L TMT for 12 h had apoptotic rates of 15.30% ± 0.75%, 18.90% ± 0.61%, 22.00% ± 0.60%, and 36.50% ± 0.66%, respectively, and the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 24 h had apoptotic rates of 28.6% ± 0.40%, 43.54% ± 2.00%, 65.73% ± 0.71%, and 74.67% ± 0.40%, respectively, all significantly higher than those of the control group (12 h: 12.80% ± 1.00%, 24h: 16.83% ± 0.25%) (P < 0.05). The ROS fluorescence intensities of the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT were 1.42, 1.71, 1.78, and 1.89 times that of the control group (P < 0.05); the PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had GSH levels of 0.17 ± 0.0, 0.20 ± 0.04, and 0.07 ± 0.03 µmol/µg protein, significantly lower than that of the control group (0.30 ± 0.01 µmol/L protein) (P < 0.05). The PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had significantly higher expression of NF-κB p65 than the control group (P < 0.05). CONCLUSION: Under our laboratory conditions, TMT can significantly inhibit proliferation and induce apoptosis in PC12 cells, which may be related to oxidative stress and NF-κB signaling pathway activation.

Cell­cell fusion as an important mechanism of tumor metastasis (Review).

Cell­cell fusion is a dynamic biological phenomenon, which plays an important role in various physiological processes, such as tissue regeneration. Similarly, normal cells, particularly bone marrow­derived cells (BMDCs), may attempt to fuse with cancer cells to rescue them. The rescue may fail, but the fused cells end up gaining the motility traits of BMDCs and become metastatic due to the resulting genomic instability. In fact, cell­cell fusion was demonstrated to occur in vivo in cancer and was revealed to promote tumor metastasis. However, its existence and role may be underestimated, and has not been widely acknowledged. In the present review, the milestones in cell fusion research were highlighted, the evidence for cell­cell fusion in vitro and in vivo in cancer was evaluated, and the current understanding of the molecular mechanisms by which cell­cell fusion occurs was summarized, to emphasize their important role in tumor metastasis. The summary provided in the present review may promote further study into this process and result in novel discoveries of strategies for future treatment of tumor metastasis.

[Protected effects of MG-132 on apoptosis induced by deltamethrin in rat's hippocampus].

OBJECTIVE: To study the protective effect of MG-132 on hippocampus cells apoptosis induced by deltamethrin (DM), one kind of pyrethroid pesticide. METHODS: 40 Male wistar rats were randomly divided into four groups: olive oil control, DM treated alone (12.5 mg/kg), MG-132 (0.5 mg/kg) plus DM group, MG-132 treated 2h plus olive oil. After 24h treatment of DM, the hippocampus was taken out to detect the apoptotic cell rate, the level of bcl-2 and Caspase-3 activity. RESULTS: Compared with DM treated alone group (27.29% +/- 2.41%), the apoptotic cell rate in MG-132 + DM group (19.94% +/- 2.07%) was increased (P < 0.05), bcl-2 expression was enhanced [(0.43 +/- 0.06) vs. (2.01 +/- 0.23)] (P < 0.05) and the activity of Caspase-3 was decreased significantly (P < 0.05) in MG-132 treated 2h plus DM group [(4.55 +/- 0.46) vs.(3.73 +/- 0.35)]. CONCLUSION: MG-132 can protect hippocampus cells against apoptosis induced by deltamethrin.

Identification of Putative UL54 (ICP27) Transcription Regulatory Sequences Binding to Oct-1, v-Myb, Pax-6 and Hairy in Herpes Simplex Viruses.

An oncolytic herpes simplex virus (oHSV) has proven amenable in oncolytic virotherapy and was approved to treat melanoma. The immediate-early (IE) protein ICP27 encoded by gene UL54 is essential for HSV infection. Post-transcriptional modification of UL54 would increase tumor targeting of oHSVs. However, UL54 gene transcription regulatory sequences and factors were not reported yet. Here we isolated a new strain LXMW of type 1 HSV (HSV-1-LXMW) in China and found it's closely related to HSV-1 strains Patton and H129 in the US by the first and next generation DNA sequencing viral DNA phylogenetic analysis. Using a weight matrix-based program Match, we found the UL54 transcription regulatory sequences binding to the transcription factors Oct-1, v-Myb and Pax-6 in HSV-1-LXMW, while the sequences binding to Oct-1 and Hairy in a HSV-2 strain. Further validation showed that HSV-1 and HSV-2 shared the common sequence binding to Oct-1, but had unique sequences to bind v-Myb and Pax-6, or Hairy, respectively, by DNA sequence alignment of total 11 HSV strains. The published results howed that the expression of transcription factors is consistent with the tissue tropism of HSV-1 and HSV-2. In the current article a new HSV-1 strain LXMW was isolated and its putative HSV UL54 transcription regulatory sequences and factors were identified for the first time. Our findings highlight the new understanding of the principles of transcriptional regulation in HSV biology and oncolytic virotherapy.

Clinicopathological features of an ascending colon mixed adenoneuroendocrine carcinoma with clinical serosal invasion.

Mixed adenoneuroendocrine carcinoma (MANEC) is exceedingly rare with a poor outcome. In this article, we reported a MANEC in a 68-year-old woman with a symptom of abdominal pain and distension. MANEC derived from the ascending colon with highly aggressive behavior. The diagnosis and distinguish of MANEC must base on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in conglobate and nested by fibrous tissue with a visible cell atypia and mitotic. NEC-like and exocrine glandular cells were also been seen in a single neoplasm. MANEC tissues were immunopositive for CK, CK20, P53, CK7, CDX-2, Ki-67 (70%+), E-cad, CD56, CEA, Syn, villin and CgA, and immunonegative for CA125, NSE, ER and PR. Here, the patient was treated by surgical operation and was followed-up near 3 months, no local recurrence and distant metastasis.

Embryonal rhabdomyosarcoma of the paranasal sinuses: a case report and review of literature.

Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy with a poor outcome. In this article, we describe a case of ERMS in the paranasal sinuses from a 60-year-old male patient. ERMS derived from the paranasal sinuses is extremely rare. The diagnosis of ERMS must be based on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in flocked sheets, cord-like and acinar-like by hyperplastic fibrous tissue. And ERMS tissues were immunopositive for myogenin, desmin, MSA, CD56, vimentin, CD99, Syn and Ki-67 (40%+), and immunonegative for CK, EMA, LCA, GFAP, NSE, S-100, HMB-45 and Melan-A. Here, the patient was treated with multimodal therapy including endoscopic surgery, chemotherapy and radiation, but the patient's postoperative recovery is not too smooth.

Malignant myoepithelioma of the breast: a case report and review of literature.

In this article, we described a malignant myoepithelioma of the breast (MMB) in a 69-year-old woman. Breast cancer derived from myoepithelial cells is very rare, usually benign. The diagnosis of MMB based on histological and immunohistochemical finding. In this case, the author diagnosed the tumor as MMB, because tumor tissues were immunopositive for 34ßE12, P63, SMA, S-100, CD10, E-Cad and Ki-67, and immunnegative for CK5/6, desmin, ER, PR and C-erbB-2, because tumor tissue showed invasive growth and local hemorrhage or necrosis, suggesting malignant, and also because there was a transition between the tumor cells and hyperplastic myoepithelium of non-tumorous ducts. The patient's postoperative recovery is smooth and regular following of patient is essential.

Ovarian sclerosing stromal tumor in a young woman with ectopic pregnancy: clinical, pathological, and immunohistochemical studies.

In this article, we described an ovarian sclerosing stromal tumor (SST) in a young woman with ectopic pregnancy. It is important to distinguish SST from fibroma, thecoma, and lipoid cell tumors clinically and histologically. Several unique histologic features including pseudolobulation, sclerosis and prominent vascularity are clearly reflected at histopathological findings. The SST cells were immunopositive for CD34, Desmin and SMA, and negative for factor VIII-related antigen, CD31, S-100, ER and PR. The patient's postoperative recovery was smooth and she was discharged after 21 days.

A case of mucoepidermoid carcinoma located in the left forearm of a middle-aged pregnant woman.

In this article, we described a mucoepidermoid carcinoma (MEC) located in the left forearm of a 39-year-old pregnant woman. Here, the patient had a superficial tip size apophysis nearly 3 years, which begin to sustained growth after pregnant in 2012, and stopped growth after childbirth. MEC is a rare malignant tumor. Previously reports showed it mainly arise from the salivary, bronchial, thyroid, breast, lacrimal gland and conjunctiva. Here, we reported a case of MEC arising from the forearm gland for the first time. Histological finding showed a cystic and solid tumor in fibrous tissue below the squamous epithelium, and some columnar or cuboidal mucous cells covering on the epidermal cells or mixed with epidermal cells included in the tumor tissues. Also, Focal hyperplasia epidermal cells with round or oval nucleus in center were distributed in small pieces but no keratosis. The tumor tissues were immunopositive for CEA, P63, ki-67 (10%), CK7 and CK5/6, and immunonegative for CK20 and GCDFP-15. This case is a low-grade MEC and the patient's postoperative recovery is smooth.

Nasopharyngeal adenoid cystic carcinoma: a case report and review of the literature.

ACC derived from nasopharyngeal epithelial cells is rare, usually benign. In this article, we reported a nasopharyngeal adenoid cystic carcinoma (NACC) in a 31-year-old woman with a symptom of hoarseness, headache, epistaxis slightly, diplopia, facial numbness and dysphagia near 3 months. A tumor on the right side of the nasopharynx was confirmed by laryngoscope check and MRI of the skull base. Histopathological findings showed that tumor cells were arranged in cord-like or acinar-like by atypical hyperplastic epithelial cells forming a cribriform and tubular pattern, and immunohistochemical findings showed that tumor tissues were immunopositive for p63 (+), CK7 (+), CK19 (+), CK8 (+), CK18 (+), SMA (+), CK (+), p53 (++), S-100 (+) and Ki-67 (5%+), and negative for CD34 (-), CK5/6 (-), CEA (-) and CD117 (-). Patient was treated by surgical operation and radiotherapy, and was followed-up near 10 months, no local recurrence and distant metastasis.

Assessing the role of IL-35 in colorectal cancer progression and prognosis.

Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.