The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model.

BACKGROUND: Microglial cells are the predominant immune cells in malignant brain tumors, but tumors may release some factors to reduce their defensive functions. Restoration of the anti-cancer function of microglia has been proposed as a treatment modality for glioblastoma. We examined the effect of intra-cranially administered recombinant adeno-associated virus encoding interleukin-12 (rAAV2/IL12) on transfection efficiency, local immune activity and survival in a rat model of glioblastoma multiforme. METHODS: F344 rats were injected with rAAV2/IL12 and implanted with syngeneic RG2 cells (glioblastoma cell line). Intracerebral interleukin-12 and interferon-γ concentrations were determined by ELISA. Activation of microglia was determined by expressions of ED1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) which were evaluated by Western blotting and immunohistochemistry. The proliferation of cancer cells was evaluated with Ki67 immunohistochemistry and apoptosis of cancer cells with TUNEL. RESULTS: The brains treated with rAAV2/IL-12 maintained high expression of interleukin-12 and interferon-γ for at least two months. In syngeneic tumor model, brains treated with rAAV2/IL12 exhibited more infiltration of activated microglia cells as examined by ED1 and TRAIL stains in the tumor. In addition, the volume of tumor was markedly smaller in AAV2/IL12-treated group and the survival time was significantly longer in this group too. CONCLUSION: The intra-cerebrally administered rAAV2/IL-12 efficiently induces long lasting expression of IL-12, the greater infiltration of activated microglia cells in the tumor associated improved immune reactions, resulting in the inhibited growth of implanted glioblastoma and the increased survival time of these rats.

Effect of Supplementation of Tanshinone IIA and Sodium Tanshinone IIA Sulfonate on the Anticancer Effect of Epirubicin: An In Vitro Study.

Tanshinone IIA (Tan IIA) and sodium tanshinone IIA sulfonate (STS) were found to have protective effects on cardiomyocyte against adriamycin-induced damage and may be used clinically. It is unclear whether the supplementation of STS or Tan IIA would affect the anticancer activity of anthracycline. To evaluate the effect of Tan IIA or STS on the anticancer of epirubicin, the cell viability, apoptosis, Akt expression, and uptake of epirubicin after supplementation of Tan IIA or STS in the epirubicin-treated BT-20 cells were measured and compared. Tan IIA inhibited BT-20 cell growth and induced apoptosis in a time- and dose-dependent manner. When Tan IIA was used with epirubicin, an increase of BT-20 cells apoptosis was accompanied by the decreasing phosphorylation of Akt. STS had no effect on the cell viability of BT-20 cells. However, when used with epirubicin, STS decreased the epirubicin-induced cytotoxicity and apoptosis in BT-20 cells. The antagonistic effect of STS on epirubicin-induced cytotoxicity in BT-20 cells occurred concomitantly with the reduced epirubicin uptake and the increased phosphorylation of Akt. STS decreased the uptake of epirubicin in BT-20 cells and blocked epirubicin-induced apoptosis through activation of Akt.

Curcumin inhibits human lung large cell carcinoma cancer tumour growth in a murine xenograft model.

Curcumin can decrease viable cells through the induction of apoptosis in human lung cancer NCI-H460 cells in vitro. However, there are no reports that curcumin can inhibit cancer cells in vivo. In this study, NCI-H460 lung tumour cells were implanted directly into nude mice and divided randomly into four groups to be treated with vehicle, curcumin (30 mg/kg of body weight), curcumin (45 mg/kg of body weight) and doxorubicin (8 mg/kg of body weight). Each agent was injected once every 4 days intraperitoneally (i.p.), with treatment starting 4 weeks after inoculation with the NCI-H460 cells. Treatment with 30 mg/kg and 45 mg/kg of curcumin or with 8 mg/kg of doxorubicin resulted in a reduction in tumour incidence, size and weight compared with the control group. The findings indicate that curcumin can inhibit tumour growth in a NCI-H460 xenograft animal model in vivo.

Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decreasing NF-kappaBp65 expression in breast cancer MDA-MB-231 cells.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is extracted from the plant Curcuma longa. It has cytotoxic effects and induces apoptosis in many human cancer cells but the molecular mechanisms are not fully understood. In the present study, we evaluated the effects of curcumin on human breast cancer MDA-MB-231 cells. The cytotoxic effects of curcumin on MDA-MB-231 cells were measured by MTT assay. The percentages of cell cycle were determined by flow cytometry. The protein expressions of p21, 53, Bax and Bcl-2 were examined by Western blotting. The results show that curcumin inhibits the proliferation of MDA-MB-231 cells and induces G2/M arrest in a dose-dependent manner. Curcumin increased the protein expressions of p21 and Bax, but decreased the protein expression of p53 and Bcl-2 in MDA-MB-231 cells. Our results show that one molecular mechanism of curcumin inhibits the proliferation of MDA-MB-231 cells either through up-regulating p21 expression and then inducing apoptosis, or through up-regulating the Bax to Bcl-2 ratio and then inducing apoptosis. Our results also show that curcumin inhibits the migratory activity of MDA-MB-231 cells through down-regulating the protein expression of NF-kappaBp65. Accordingly, the therapeutic potential of curcumin for breast cancer deserves further study.

Tanshinone IIA down-regulates the protein expression of ErbB-2 and up-regulates TNF-alpha in colon cancer cells in vitro and in vivo.

Tanshinone IIA (Tan-IIA) was isolated from Salviae Miltiorrhizae Radix. Our previous studies showed that Tan-IIA induced apoptosis in human colon cancer colo 205 cells, but the molecular mechanisms of the effect of Tan-IIA on human colon cancer were not clearly elucidated. The protein expression of ErbB-2 was up-regulated and activated in human and experimental colon cancers. In the present study, the effects of Tan-IIA on the protein expression of ErbB-2 in colo 205 cells were investigated. In vitro, colo 205 cells were treated with various concentrations of Tan-IIA (1, 2 and 5 mug/ ml) for 24 h, and the protein expression of TNF-alpha, ErbB-2 and caspase-3 was assayed by Western blotting. For the in vivo studies, male SCID mice were xenografted with colo 205 cells, and from day 10, Tan IIA (20 mg/kg/day, dissolved in corn oil) was administered by oral feeding for 30 days. As a control, mice with xenografted tumors were separately treated with corn oil (0.1 ml/10 g body weight). Expression of TNF-alpha, ErbB-2 and caspase-3 proteins was measured by Western blot analysis. Our results showed that Tan-IIA down-regulated the protein expression of ErbB-2 and up-regulated TNF-alpha and caspase-3 in colo 205 cells in vitro. In a colo 205 xenograft model, treatment with Tan-IIA caused up-regulation of TNF-alpha, caspase-3 and down-regulation of ErbB-2 protein expression as compared to the controls. Based on these observations, one possible molecular mechanisms by which Tan-IIA inhibits the proliferation of colo 205 cells is through the down-regulation of ErbB-2 protein expression and the up-regulation of the protein expression of TNF-alpha and caspase-3.

Tanshinone IIA inhibits human breast cancer cells through increased Bax to Bcl-xL ratios.

Tanshinone IIA (C19H18O3) was extracted from danshen (Salviae miltiorrhizae radix). It has cytotoxic properties and induces apoptosis in many human cancer cells. The molecular mechanisms are poorly understood, therefore, in the present study, we aimed to elucidate its anticancer activity on human breast cancer MDA-MB-231 cells. The cytotoxic effects of tanshinone IIA on MDA-MB-231 cells were measured by MTT assay. The percentages of cells in different cell cycle phases were determined by flow cytometry. The protein expression of Bax and Bcl-2 was examined using Western blotting. The results showed that tanshinone IIA inhibits the proliferation of MDA-MB-231 cells in a dose- and time-dependent manner. Tanshinone IIA induces apoptosis in a dose-dependent manner and the percentage of cells in sub-G1 phase. It increases the protein expression of Bax but decreases the Bcl-2 expression in MDA-MB-231 cells. Our findings suggest that tanshinone IIA can inhibit the proliferation of MDA-MB-231 cells by active apoptosis. One of the mechanisms may be through up-regulating the expression of Bax but down-regulating Bcl-2 expression and then inducing apoptosis. In conclusion, tanshinone IIA has therapeutic potential in breast cancer patients.

Growth inhibition and apoptosis induction by tanshinone I in human colon cancer Colo 205 cells.

Tanshinone I (Tan-I) and tanshinone IIA (Tan-IIA) were isolated from Danshen (Salviae Miltiorrhizae Radix), a widely prescribed traditional herbal medicine that is used to treat cardiovascular and dysmenorrhea diseases. In our previous study, Tan-IIA was demonstrated to induce apoptosis in human colon cancer Colo 205 cells. However, the effect of Tan-I on human colon cancer cells is not clearly understood yet. In this study, the anti-growth and apoptosis-eliciting effects of Tan-I, as well as its cellular mechanisms of actions, were investigated in Colo 205 human colon cancer cells. Tan-I reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and in cells in the sub-G1 fraction. The expression of p53, p21, bax and caspase-3 increased in Tan-I-treated cells. In addition, the cell cycle analysis showed G0/G1 arrest. These findings suggest that Tan-I induces apoptosis in Colo 205 cells through both mitochondrial-mediated intrinsic cell-death pathways and p21-mediated G0/G1cell cycle arrest. Accordingly, the therapeutic potential of Tan-I for colon cancer deserves further study.

Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205).

The effects of the crude extract of Solanum lyratum (SLE) on human colon cancer colo 205 cells were investigated. The cell viability, morphological changes of the cells, cell cycle arrest, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (deltapsi(m)) and cell cycle- and apoptosis-associated protein levels and gene expressions were examined in colo 205 cells after exposure to various concentrations of SLE for different time periods. The results indicated that SLE decreased the percentage of viable colo 205 cells accompanied by morphological changes. The most effective concentration of SLE was 300 pg/ml (SLE 300) and this concentration was used for further investigations. SLE induced S-phase arrest and apoptosis (sub-G1) in the colo 205 cells and those effects were dose- and time-dependent. DAPI staining and DNA gel electrophoresis confirmed that SLE induced apoptosis in colo 205 cells. Flow cytometric analysis also showed that SLE 300 promoted ROS production and decreased the deltapsi(m). Western blotting analysis indicated that SLE 300 increased Bax levels and decreased Bcl-2 levels, which caused the loss of deltapsi(m) followed by cytochrome c release and caspase-9 and -3 activation, finally leading to apoptosis. SLE 300 also promoted p53 and p27, but decreased the levels of cyclin B1 thus causing S-phase arrest. The gene expression associated with those proteins was also confirmed by PCR methods. The findings show that SLE might be used as a colon cancer therapeutic agent in the future.

Curcumin inhibits WEHI-3 leukemia cells in BALB/c mice in vivo.

Curcumin (1, 7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5- dione), a natural polyphenol product of the plant Curcuma longa, exhibited potent inhibitory activities against proliferation, induced cell cycle arrest and exhibited the induction of apoptosis in several tumor cell lines. In our previous studies, we have shown that curcumin induced cell cycle arrest and apoptosis on human leukemia HL-60 and mouse leukemia WEHI-3 cells; there are no reports regarding whether or not it affects leukemia cells in vivo. In the present study, we investigated the effects of curcumin on WEHI-3 in BALB/c mice and the results indicated that curcumin reduces the percentage of Mac-3 marker, which is the precursor of macrophage. Curcumin induced significant effects on the population of B cells from murine leukemia in vivo. We also investigated the weights of spleen and liver from murine leukemia and the results showed that curcumin reduced the weight of the liver and spleen. From the pathological examinations, the effects of curcumin on the liver and spleen from mice after being injected with WEHI-3 cells were apparent. Both organs were enlarged. In conclusion, curcumin affect WEHI-3 cells in vivo.

Effects of curcumin on N-bis(2-hydroxypropyl) nitrosamine (DHPN)-induced lung and liver tumorigenesis in BALB/c mice in vivo.

Curcumin (diferuloylmethane), a phenolic compound from the plant Curcuma longa (Linn.) has been shown to exhibit antitumor activity and apoptosis in many human cancer cell lines including that of lung and liver cancer. In this study, curcumin was evaluated in BALB/c mice for its ability to inhibit pulmonary and liver adenoma formation and growth after they were orally treated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Animals were treated with DHPN in water for approximately 14 days before multiple doses of curcumin were given intraperitoneally. It was found that 200 microM curcumin reduced lung and liver tumor multiplicity by 37% (p<0.05) and 30% (p<0.05) respectively. The results indicated that curcumin significantly inhibited pulmonary and liver adenoma formation and growth in BALB/c mice. The precise mechanism by which curcumin inhibits lung and liver tumorigenesis remains to be elucidated. Thus, curcumin appears to be a promising new chemotherapeutic and preventive agent for lung and liver cancer induced by DHPN.

Tanshinone IIA can inhibit MiaPaCa­2 human pancreatic cancer cells by dual blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways.

Tanshinone IIA (Tan­IIA; C19H18O3) is derived from Danshen (the roots of Salvia miltiorrhiza), and has been reported to possess anti­inflammatory and antioxidant activities. Tan­IIA can inhibit BxPC­3 human pancreatic cancer cells in vitro through inducing endoplasmic reticulum stress and apoptosis via mitochondrial pathways. However, the efficacy and molecular mechanisms of Tan­IIA in human pancreatic cancer have not yet been elucidated. The transmembrane tyrosine kinases, including insulin­like growth factor 1 receptor (IGF1R), vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor (EGFR) have been implicated in the survival and metastasis of cancer. In addition, the Ras/Raf/mitogen­activated protein kinase kinase (MEK)/extracellular signal­regulated kinase (ERK) and phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways are the most commonly dysregulated kinase cascades in human cancer. The present study aimed to investigate the efficacy and molecular mechanisms of Tan­IIA in MiaPaCa­2 human pancreatic carcinoma cells. The protein expression levels of EGFR, IGF1R, VEGFR, Ras, PI3K, AKT, mTOR, Raf, MEK, ERK and phosphatase and tensin homolog (PTEN) were detected in Tan­IIA­treated MiaPaCa­2 cells by western blotting. The results demonstrated that the protein expression levels of EGFR, IGF1R, VEGFR, Ras, Raf, MEK, ERK, PI3K, AKT, mTOR and PTEN were decreased in MiaPaCa­2 cells treated with various concentrations of Tan­IIA for different durations. In conclusion, these findings indicated that Tan­IIA may inhibit MiaPaCa­2 human pancreatic cancer cells; the molecular mechanisms underlying this inhibitory effect may be involved in downregulating EGFR, IGF1R and VEGFR expression, and dual blockade of the Ras/Raf/MERK/ERK and PI3K/AKT/mTOR pathways.

Tanshinone IIA inhibits gastric carcinoma AGS cells by decreasing the protein expression of VEGFR and blocking Ras/Raf/MEK/ERK pathway.

The RAS/RAF/MEK/ERK pathway is one of the most frequently dysregulated kinase cascades in human cancer, that facilitate the proliferation and survival of cancers driven by growth factor receptors. Tanshinone IIA (Tan-IIA) was extracted from Danshen (Salviae Miltiorrhizae Radix). Tan-IIA inhibition of the proliferation of gastric cancer are well documented, but the molecular mechanisms of Tan-IIA inhibition of gastric cancer have not been well elucidated. We evaluated the protein expression of vascular epidermal growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2), Ras, Raf, MEK, ERK, PARP, caspase-3 and ß-actin in AGS cells by western blotting. The results showed that AGS cells treated with Tan-IIA upregulated the protein expression of PARP and caspase-3 but decreased VEGFR, HER2, Ras, Raf, MEK and ERK time- and dose-dependently. These findings demonstrated that Tan-IIA inhibited human gastric cancer AGS cells; one of the molecular mechanisms may be through decreasing the protein expression of VEGFR and HER2, then blocking the Ras/Raf/MEK/ERK pathway to induce the activation of PARP and caspase-3 to induce apoptosis.

Stapled hemorrhoidectomy versus conventional excision hemorrhoidectomy for acute hemorrhoidal crisis.

We compared the safety and clinical outcomes of stapled hemorrhoidectomy and conventional excision hemorrhoidectomy in the treatment of acute hemorrhoidal crisis, and analyzed various factors associated with complications in stapled hemorrhoidectomy. Forty patients underwent stapled hemorrhoidectomy and forty underwent conventional excision hemorrhoidectomy. All had the operation under local anesthesia with conscious sedation within 24 h of admission. The length of surgery, hospital stay, disability, postoperative pain, and the use of analgesics were significantly less for patients in the stapled hemorrhoidectomy group. Stapled hemorrhoidectomy did not significantly increase the rate of complications. Five patients in the stapled group (12.5%) required further surgical intervention: three with thrombosed hemorrhoids and two with recurrent prolapse. No serious complications were reported in either group. Patient satisfaction was similar in the two groups. Increased age was identified as a factor that significantly elevated the risk of complications in the stapled group (OR, 1.06; 95% CI, 1.01-1.13). Anemia and time between the onset of prolapsed hemorrhoids and hospital admission were also risk factors for complications, although they were not significant. Stapled hemorrhoidectomy is a feasible treatment for selected patients with an acute hemorrhoidal crisis and has a similar complication rate to that of conventional excision hemorrhoidectomy. Stapled hemorrhoidectomy is superior in less-postoperative pain, shorter operation time, shorter hospital stay, and earlier return to normal activity. However, we suggest that older patients with anemia or a prolonged hemorrhoidal crisis are unsuitable for stapled hemorrhoidectomy.

The role of Ca+2 on rhein-induced apoptosis in human cervical cancer Ca Ski cells.

Apoptosis induced by rhein, an active component of senna, has been reported in various human cancer cells, however, its molecular mechanisms are not precisely known. In this study, the mechanisms of apoptosis by which rhein acts on human cervical cancer Ca Ski cells were examined. Flow cytometric analysis demonstrated that rhein induced the abrogation of mitochondrial membrane potential (MMP) and cleavage of Bid protein. Rhein also induced an increase in the levels of Fas, p53, p21 and Bar, but a decrease in the level of Bcl-2. The activities of both caspase-8 and -9 were enhanced by rhein, promoting caspase-3 activation, leading to DNA fragmentation, thus, indicating that rhein-induced apoptosis is caspase-dependent. In addition, rhein induced an increase in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (a calcium chelator). BAPTA attenuated the MMP abrogation and significantly dinimished the occurrence of rhein-induced apoptosis in Ca Ski cells. In conclusion, our data demonstrate that rhein-induced apoptosis occurs via a caspase-dependent and mitochondria-dependent pathway which is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.

Crude extracts of Euchresta formosana radix inhibit invasion and migration of human hepatocellular carcinoma cells.

Crude extracts of Euchresta formosana radix (EFR) have previously been observed to induce the suppression of liver cancer Hep3B cell growth and induce apoptosis in response to overexpression of reactive oxygen species, GADD153, Bax and caspase-3, and to decrease the levels of mitochondrial membrane potential in vitro. In this study, the effect of EFR on cell migration and invasion by the human liver hepatocellular carcinoma (HCC) cell line Hep3B was examined. Hep3B cells treated in vitro with EFR migrated and invaded less than cells treated with phosphate-buffered saline (PBS) as a control. EFR inhibited migration and invasion by down-regulating the production of RhoA and ROCK1, FAK, and matrix metalloproteinase-1, -2, -9 and -10 relative to PBS only. These results show that EFR inhibits invasion and migration by liver cancer cells by down-regulating proteins associated with these processes, resulting in reduced metastasis. Thus, EFR should be considered as a possible therapeutic agent for inhibiting primary tumor growth and preventing metastasis.

Crude extracts of Euchresta formosana radix induce cytotoxicity and apoptosis in human hepatocellular carcinoma cell line (Hep3B).

In this study, the effects of 95% ethanol extracts of Euchresta formosana radix (EFR) on the cell cycle and apoptosis in human hepatocellular carcinoma (HCC) Hep3B cells were investigated. The results indicated that EFR decreased DNA synthesis and viable Hep3B cell numbers in a concentration-dependent manner. EFR induced a p21- and p27-dependent cell cycle arrest in S-phase and apoptosis of the Hep3B cells. The induction of apoptosis by EFR treatment was also confirmed by DAPI staining. EFR inhibited cyclin-dependent kinase (CDK)-1 and -2 expression and decreased cyclin B1 and E levels, resulting in S-phase arrest. EFR induced reactive oxygen species (ROS) production followed by endoplasmic reticulum (ER) stress that was based on the increase of GADD153 and GRP78 which led to the release of Ca2+ in the Hep3B cells. The EFR-promoted apoptosis was associated with increasing activation of caspases 3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and increased expression of p21(CIP1/WAF1), p27(KIP1), Bax and Bad. Furthermore, the levels of Bcl-xl decreased after EFR treatment. Alteration of these key anti- and pro-apoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in the Hep3B cells.

GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells.

Berberine, an isoquinoline alkaloid, has been shown to possess anticancer properties in some cancer cell lines. Here, we report that in vitro treatment of cervical cancer Ca Ski cells with berberine decreased the percentage of viable Ca Ski cells in a dose-dependent and time-dependent manner. Berberine enhanced the apoptosis of Ca Ski cells with the induction of a higher ratio of p53 and Bax/Bcl-2 proteins, increased levels of reactive oxygen species (ROS) and Ca2+, disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.

Tanshinone IIA increases protein expression levels of PERK, ATF6, IRE1α, CHOP, caspase­3 and caspase­12 in pancreatic cancer BxPC­3 cell­derived xenograft tumors.

Tanshinone (Tan)-IIA is a derivative of phenanthrenequinone and the main active ingredient isolated from Salviae miltiorrhizae radix (Danshen). Previous studies have demonstrated that Tan­IIA increased the protein expressions levels of protein kinase RNA­like endoplasmic reticulum kinase (PERK), activating transcription factor (ATF) 6, caspase­12 and CCAAT­enhancer­binding protein homologous protein (CHOP), to induce endoplasmic reticulum (ER) stress and apoptosis in human pancreatic cancer BxPC­3 cells. However, to the best of our knowledge, the effects of Tan­IIA on pancreatic cancer cells have not been investigated in vivo. Further studies are required to elucidate the therapeutic potential of Tan­IIA in inducing ER stress in cancer cells in vivo. The present study aimed to investigate the effects of Tan­IIA on the expression of ER stress­related proteins in BxPC­3­derived xenograft tumors. A total of 30 male severe combined immunodeficiency mice (age, 4 weeks) were implanted with BxPC­3 cells (2x106/0.2 ml) and subsequently treated with various doses of Tan­IIA (0, 30 and 90 mg/kg) for 4 weeks. After mice were sacrificed on day 33, the xenograft tumors were dissected and total protein was extracted for western blot analysis. The results of the present study demonstrated that Tan­IIA inhibited the growth of BxPC­3­derived xenograft tumors. In addition, Tan­IIA increased the protein expression levels of PERK, ATF6, caspase­12, inositol­requiring enzyme (IRE) 1α, eukaryotic initiation factor (eIF) 2α, phosphorylated (p)­c­Jun N­terminal kinase (JNK), CHOP and caspase­3 in a dose­dependent manner. These results indicated that Tan­IIA induced ER stress via increasing the protein expression levels of PERK, ATF6, caspase­12, IRE1α, eIF2α, p­JNK, CHOP and caspase­3 in BxPC­3 cells in vivo. Therefore, it may be hypothesized that Tan­IIA has potential for the development of novel therapeutic strategies for the treatment of patients with pancreatic cancer.

Effect of Lipodox in combination with bevacizumab in a patient with a metastatic malignant phyllodes breast tumor: A case report.

A 76-year-old female patient with a malignant phyllodes tumor underwent modified radical mastectomy and wide excision. Multiple nodules were observed in the operated wound area. Positron emission tomography-computed tomography (PET-CT) revealed recurrent disease in the left breast, the adjacent left third rib, the left internal mammary region and the left ilium. A novel formulation of bevacizumab (5 mg/m2, first day) in combination with liposomal doxorubicin (Lipodox, 30 mg/m2, second day) was administered for 3 cycles every 2 weeks, and subsequently wide excision was performed. Lipodox (40 mg/m2) was administered for 3 cycles every 3 weeks, starting 4 weeks after the surgery. Follow-up whole body PET-CT scanning, 3 and 6 months later, indicated no sign of residual hypermetabolic malignancy. Malignant phyllodes tumors do not usually respond to chemotherapy or radiotherapy. In the present case report, a novel formulation of bevacizumab in combination with Lipodox was administered as neoadjuvant chemotherapy in a patient with a malignant phyllodes tumor and preoperative tumor shrinkage was achieved, resulting in clear resection margins.

Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions.

Curcumin (diferuloylmethane) is a chemical derived from several Curcuma species (turmeric), possessing anti-inflammatory and antioxidant properties and which, thus, may be a potential anticancer drug. However, its mechanism of action is not fully understood. Our previous studies had shown that curcumin induced cytotoxicity, cell cycle arrest and apoptosis in human colon cancer colo 205 cells. In this study, curcumin affected the levels of NF-kappaB/ p65 in a time-dependent manner but did not affect NF-kappaB/ p50, based on Western blotting methods. In vitro experiments revealed that curcumin inhibited Cox-2 levels, but promoted those of Cox-1 in colo 205 cells. Curcumin also inhibited MMP-2 levels and promoted MMP-9 levels, but did not affect MMP-7 levels, based on Western blotting assays. These effects were also confirmed by cDNA microarray. Remarkably, curcumin not only exerted its effect on the protein levels of NF-kappaB, Cox-1 and -2, MMP-2 and -7, but also directly inhibited their mRNA levels. Curcumin was also found to significantly repress the in vitro invasion of colo 205 cells.