International Journal of Cancer via MedWorm.com

GB virus C infection and non-Hodgkin lymphoma: important to know but the jury is out

International Journal of Cancer — Tue, 16 Mar 2010 00:00:00 +0100

No abstract. (Source: International Journal of Cancer)

Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth

International Journal of Cancer — Tue, 16 Mar 2010 00:00:00 +0100

Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. We have shown that flavokawain B (FKB), a kava chalcone, is about 4- to 12-fold more effective in reducing the cell viabilities of androgen receptor (AR)-negative, HRPC cell lines DU145 and PC-3 than AR-positive, hormone-sensitive prostate cancer cell lines LAPC4 and LNCaP, with minimal effect on normal prostatic epithelial and stromal cells. FKB induces apoptosis with an associated increased expression of proapoptotic proteins: death receptor-5, Bim and Puma and a decreased expression of inhibitors of apoptosis protein: XIAP and survivin. Among them, Bim expression was signifi...

CCR9 mediates PI3K/AKT-dependent antiapoptotic signals in prostate cancer cells and inhibition of CCR9-CCL25 interaction enhances the cytotoxic effects of etoposide

International Journal of Cancer — Fri, 12 Mar 2010 00:00:00 +0100

In this study, we show that CC chemokine receptor-9 (CCR9) and its natural ligand CCL25 interaction upregulates antiapoptotic proteins (i.e., PI3K, AKT, ERK1/2 and GSK-3[beta]) and downregulate activation of caspase-3 in PCa cells. Significant downregulation of these CCR9-mediated antiapoptotic proteins in the presence of a PI3K inhibitor (wortmannin), further suggests that the antiapoptotic action of CCR9 is primarily regulated through PI3K. Furthermore, the cytotoxic effect of etoposide was significantly inhibited in the presence of CCL25, and this inhibitory effect of CCL25 was abrogated when CCR9-CCL25 interaction was blocked using anti-CCR9 monoclonal antibodies. In conformation to these in vitro studies, significant reduction in tumor burden was found in mice receiving CCL25 neutrali...

The antitumor activity of the fungicide ciclopirox

International Journal of Cancer — Thu, 11 Mar 2010 00:00:00 +0100

Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231) and colon adenocarcinoma (HT-29) cells in a concentration-dependent manner. By cell cycle analysis, CPX induced accumulation of cells in G1/G0 phase of the cell cycle. Concurrently, CPX downregulated cellular protein expression of cyclins (A, B1, D1 and E) and cyclin-dependent kinases (CDK2 and CDK4) and upregulated expression of the CDK inhibitor...

The health and economic effects of HPV DNA screening in The Netherlands

International Journal of Cancer — Wed, 10 Mar 2010 00:00:00 +0100

We studied the health and economic effects of human papillomavirus (HPV) DNA testing in cervical screening using a simulation model. The key data source was a Dutch longitudinal screening trial. We compared cytological testing with repeat cytology (for borderline/mildly abnormal smears) to HPV testing with cytology triage (for HPV-positive smears), combination testing (combined HPV and cytology) and cytological testing with HPV triage (for borderline/mildly abnormal smears). We varied the screening interval from 5 to 10 years. The main outcome measures were the number of cervical cancer cases, the number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The base-case estimates were accompanied with ranges across 118 calibrated parameter settings (...

Silencing of the UCHL1 gene in giant cell tumors of bone

International Journal of Cancer — Wed, 03 Mar 2010 00:00:00 +0100

Giant cell tumors are heterogeneous tumors consisting of multinucleated giant cells, fibroblast-like stromal cells and mononuclear histiocytes. The stromal cells have been identified as the neoplastic cell population, which promotes the recruitment of histiocytes and the formation of giant cells. Strong evidence exists that these cells develop from mesenchymal stem cells (MSCs) but little is known about the molecular mechanisms involved in GCT tumorigenesis. The aim of our study was the identification of cancer-related genes differentially expressed in GCTs compared to MSCs in order to identify possible targets for aberrant promoter methylation, which may contribute to MSC transformation and GCT development. Gene expression of 440 cancer-related genes was analyzed by DNA microarrays in GCT...

Tumors exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination

International Journal of Cancer — Mon, 01 Mar 2010 00:00:00 +0100

Clinical studies have shown that patients with highly hypoxic primary tumors may have poor disease-free and overall survival rates. Studies of experimental tumors have revealed that acutely hypoxic cells may be more metastatic than normoxic or chronically hypoxic cells. In the present work, causal relations between acute cyclic hypoxia and metastasis were studied by periodically exposing BALB/c nu/nu mice bearing A-07 human melanoma xenografts to a low oxygen atmosphere. The hypoxia treatment consisted of 12 cycles of 10 min of 8% O2 in N2 followed by 10 min of air for a total of 4 hr, began on the first day after tumor cell inoculation and was given daily until the tumors reached a volume of 100 mm3. Twenty-four hours after the last hypoxia exposure, the primary tumors were subjected to d...

Functional screening identifies a microRNA, miR-491 that induces apoptosis by targeting Bcl-XL in colorectal cancer cells

International Journal of Cancer — Fri, 26 Feb 2010 00:00:00 +0100

MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate expression of target mRNA. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and considered as new therapeutic targets for cancers. In our study, we performed a gain-of-function screen using 319 miRNAs to identify those affecting cell proliferation and death in human colorectal cancer cells (DLD-1). We discovered a number of miRNAs that increased or decreased cell viability in DLD-1. They included known oncogenic miRNAs such as miR-372 and miR-373, and tumor suppressive miRNAs such as miR-124a, but also some for which this information was novel. Among them, miR-491 markedly decreased cell viability by inducing apoptosis. We demonstrated that Bcl-XL was ...

The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification

International Journal of Cancer — Sun, 21 Feb 2010 00:00:00 +0100

In conclusion, these data suggest that elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in NB, offering new insights into PA pathways and PA metabolism-targeting therapy in NB. (Source: International Journal of Cancer)

Elevated lung cancer risk is associated with deficiencies in cell cycle checkpoints: genotype and phenotype analyses from a case-control study

International Journal of Cancer — Wed, 17 Feb 2010 00:00:00 +0100

This study provides evidence that a less efficient G2/M checkpoint is significantly associated with lung cancer risk in African American women. The data also suggested that the function of G2/M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control. (Source: International Journal of Cancer)

Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing ability

International Journal of Cancer — Tue, 16 Feb 2010 00:00:00 +0100

We previously demonstrated that Pim-3, a protooncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not in normal tissues of endoderm-derived organs, including pancreas, liver, colon and stomach. Moreover, aberrantly expressed Pim-3 can prevent tumor cell apoptosis by inactivating a proapoptotic molecule, Bad, and enhancing the expression of an antiapoptotic molecule, Bcl-XL. These observations prompted us to speculate that a chemical targeting Pim-3 kinase may be a good candidate for a novel type of anticancer drug. Hence, we screened various low-molecule compounds by examining their capacity to inhibit Pim-3 kinase activity in vitro. We observed that some synthetic intermediates of stemonamide can inhibit in vitro activities of Pim-3 kinase and...

Targeted knockdown of Bcl2 in tumor cells using a synthetic TRAIL 3[prime]-UTR microRNA

International Journal of Cancer — Wed, 10 Feb 2010 00:00:00 +0100

This study proves a general paradigm for cancer therapy by using 3[prime] UTR microRNA technology. (Source: International Journal of Cancer)

Erratum

International Journal of Cancer — Tue, 09 Feb 2010 00:00:00 +0100

No abstract (Source: International Journal of Cancer)

Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas

International Journal of Cancer — Tue, 09 Feb 2010 00:00:00 +0100

Overexpression of ERCC1 mRNA is associated with drug resistance to cisplatin in human gliomas, but the role of the ERCC1 promoter in drug resistance has not been demonstrated. We have used sodium bisulfite sequencing to compare ERCC1 promoter methylation patterns in cisplatin-sensitive and cisplatin-resistant glioma cells. The levels of ERCC1 DNA methylation, mRNA and protein in 32 human glioma samples were examined by methylation specific PCR, real-time RT-PCR and immunohistochemistry, respectively. Meanwhile, cisplatin sensitivities to these human glioma samples were tested by histoculture drug response assay. Hypermethylation was observed in the upstream 5Kb region of the ERCC1 promoter of cisplatin-sensitive glioma cell lines. ERCC1 DNA methylation levels were highly variable in 32 hum...

Pak1 and Pak2 are activated in recurrent respiratory papillomas, contributing to one pathway of Rac1-mediated COX-2 expression

International Journal of Cancer — Wed, 03 Feb 2010 00:00:00 +0100

Recurrent respiratory papillomas are premalignant tumors of the airway caused by human papillomaviruses (HPVs), primarily Types 6 and 11. We had reported that respiratory papillomas overexpress the epidermal growth factor receptor (EGFR), the small GTPase Rac1 and cyclooxygenase-2 (COX-2), and have enhanced nuclear factor-[kappa]B (NF[kappa]B) activation with decreased levels of I[kappa]B-[beta] but not I[kappa]B-[alpha]. We also showed that EGFR-activated Rac1 mediates expression of COX-2 through activation of p38 mitogen-activated protein kinase. We have now asked whether the p21-activated kinases Pak1 or Pak2 mediate activation of p38 by Rac1 in papilloma cells. Pak1 and Pak2 were constitutively activated in vivo in papilloma tissue compared with normal epithelium, and Rac1 siRNA reduce...

Selective concomitant inhibition of mTORC1 and mTORC2 activity in estrogen receptor negative breast cancer cells by BN107 and oleanolic acid

International Journal of Cancer — Wed, 03 Feb 2010 00:00:00 +0100

Hormonal, targeted and chemotherapeutic strategies largely depend on the expression of their cognate receptors and are often accompanied by intolerable toxicities. Effective and less toxic therapies for estrogen receptor negative (ER-) breast cancers are urgently needed. Here, we present the potential molecular mechanisms mediating the selective pro-apoptotic effect induced by BN107 and its principle terpene, oleanolic acid (OA), on ER- breast cancer cells. A panel of breast cancer cell lines was examined and the most significant cytotoxic effect was observed in ER- breast lines. Apoptosis was the major cellular pathway mediating the cytotoxicity of BN107. We demonstrated that sensitivity to BN107 was correlated to the status of ER[alpha]. Specifically, the presence of functional ER[alpha]...

Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and C/EBP[alpha] during oral cancer suppression

International Journal of Cancer — Tue, 02 Feb 2010 00:00:00 +0100

Curcumin is a common food ingredient derived from the plant Curcuma longa and is a potent drug against tumorigenesis. Both insulin-like growth factor binding protein-5 (IGFBP-5) and CCAAT/enhancer-binding protein [alpha] (C/EBP[alpha]) are suppressors of head and neck carcinogenesis. We identified curcumin as an inducer of IGFBP-5 expression in multiple types of oral keratinocytes; furthermore, curcumin induces IGFBP-5 promoter activity in SAS oral cancer cells. Promoter deletion mapping identified a region (nt -71 to nt -59 relative to the transcription start site) as containing a C/EBP[alpha]-binding element that is indispensable for curcumin-mediated IGFBP-5 upregulation. Chromatin immunoprecipitation assays revealed that in vivo binding of C/EBP[alpha] to this region was remarkably inc...

Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma

International Journal of Cancer — Tue, 02 Feb 2010 00:00:00 +0100

TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of [Delta]Np63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to ad...

Alcohol consumption-associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center-based Prospective Study

International Journal of Cancer — Sat, 30 Jan 2010 00:00:00 +0100

Epidemiological studies have evaluated whether the impact of alcohol intake on breast cancer risk is modified by use of exogenous estrogens, folate intake, body weight and smoking status, but results have been inconsistent. Further, effect modification by intake of isoflavones and alcohol-induced facial flushing, which are prevalent in Asian populations, have not been investigated. We investigated the association between alcohol intake and breast cancer risk and whether the association is modified by these factors among 50,757 premenopausal and postmenopausal women (aged 40-69 years) in the population-based Japan Public Health Center-based Prospective Study. Alcohol consumption and other related factors were assessed using self-reported questionnaires. Through to the end of 2006, 572 patie...

Promoter hypomethylation and upregulation of trefoil factors in prostate cancer

International Journal of Cancer — Thu, 28 Jan 2010 00:00:00 +0100

Trefoil factors, mucin-associated peptides, are overexpressed in prostate cancer (PC). We hypothesized that promoter methylation contributes to the regulation of trefoil factors (TFF1, TFF2 and TFF3) in human prostate cells. Here we show hypomethylation of promoter regions of TFF1 and TFF3 in PC cell lines with significant TFF expression as compared to benign immortalized prostate cell lines and PC cell lines not expressing trefoil factor. The most striking difference was observed for CpG sites located close to the AUG start codon overlapping several putative binding sites for cellular transcription factors. TFF2 was hypermethylated and had no or very low expression in all prostate cell lines investigated. Treatment of methylated cell lines with 5-aza-2[prime]-deoxycytidine restored TFF ex...

Serum levels of vitamin D, PTH and calcium and breast cancer risk - a prospective nested case-control study

International Journal of Cancer — Thu, 28 Jan 2010 00:00:00 +0100

We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels...

Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers

International Journal of Cancer — Thu, 28 Jan 2010 00:00:00 +0100

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladd...

Chemo-radiotherapy for advanced non-small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

International Journal of Cancer — Thu, 28 Jan 2010 00:00:00 +0100

There has been conflicting evidence concerning the best sequence of radiotherapy (RT) and chemotherapy (CT) for advanced non-small-cell-lung-cancer (NSCLC). To investigate whether current clinical trials can clarify this schedule and offer further bases for clinical decision making, we performed a systematic review of 11 trials (2,043 patients; concurrent-1,019, sequential-1,024) that compared concurrent RT-CT with sequential arm in advanced NSCLC patients. Primary end point was overall survival (OS). Pooled median ratios (MRs) and progression-free-survival ratios (FRs) for median survival and progression-free survival (PFS) were calculated using the weighted sum of the log ratio of MR and FR of individual study. Pooled odds ratios (ORs) for the objective response rate, relapse control rat...

Insulin-like growth factor-1 receptor as a novel prognostic marker and its implication as a cotarget in the treatment of human adenocarcinoma of the esophagus

International Journal of Cancer — Tue, 26 Jan 2010 00:00:00 +0100

Insulin-like growth factor-1 receptor (IGF-1R) and human epidermal growth factor receptor-2 (HER2) receptor expression has been found to be a key regulator of tumorigenesis. The purpose of our study was to establish the prognostic significance of IGF-1R in esophageal cancer and to determine the effect of IGF-1R and HER2 targeting with [alpha]-IR3 and HerceptinTM antibodies on the proliferation of esophageal cancer cells in vitro. IGF-1R expression and clinicopathological correlations were analyzed with a tissue microarray containing 234 esophageal cancer specimens (133 adenocarcinomas and 101 squamous cell carcinomas). Proliferation changes associated with HerceptinTM and [alpha]-IR3 blockage were evaluated with the unique human esophageal cancer cell lines Pt1590 and LN1590. IGF-1R and HE...

Ewing's sarcoma cells with CD57-associated increase of tumorigenicity and with neural crest-like differentiation capacity

International Journal of Cancer — Tue, 26 Jan 2010 00:00:00 +0100

The Ewing family of tumors (EFT) is an important group of pediatric malignancies with a guarded prognosis. Little is known about the heterogeneity of EFT cells, and the cellular origin of EFT is disputed. We now add evidence that EFT are heterogeneous by showing that EFT cells from spheres growing in serum-free medium are markedly more tumorigenic than adherently growing EFT cells. Furthermore, EFT cells strongly expressing CD57 (HNK-1), a surface marker for migrating and proliferating neural crest cells, are more tumorigenic than cells with low expression of CD57, possibly mediated in part by enhanced adhesion and invasion. We contribute to the controversy about the cellular origin of EFT by clonal analysis, showing that EFT cells can differentiate similar to neural crest cells. These dat...

Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: A postintervention follow-up in the SU.VI.MAX Study

International Journal of Cancer — Tue, 26 Jan 2010 00:00:00 +0100

In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow-up. (Source: International Journal of Cancer)

Performance of diagnostic mammography differs in the United States and Denmark

International Journal of Cancer — Tue, 26 Jan 2010 00:00:00 +0100

Diagnostic mammography is the primary imaging modality to diagnose breast cancer. However, few studies have evaluated variability in diagnostic mammography performance in communities, and none has done so between countries. We compared diagnostic mammography performance in community-based settings in the United States and Denmark. The performance of 93,585 diagnostic mammograms from 180 facilities contributing data to the US Breast Cancer Surveillance Consortium (BCSC) from 1999 to 2001 was compared to that of all 51,313 diagnostic mammograms performed at Danish clinics in 2000. We used the imaging workup's final assessment to determine sensitivity, specificity and an estimate of accuracy: area under the receiver-operating characteristics (ROCs) curve (AUC). Diagnostic mammography had slig...

Inhibition of Met/HGF receptor and angiogenesis by NK4 leads to suppression of tumor growth and migration in malignant pleural mesothelioma

International Journal of Cancer — Tue, 26 Jan 2010 00:00:00 +0100

NK4 exhibits two distinct biological actions: antagonistic inhibition of hepatocyte growth factor (HGF) through binding to the Met/HGF receptor, and antiangiogenic action through binding to perlecan. Here, the anti-tumor effect of NK4 on malignant pleural mesothelioma was investigated. Of the 7 human malignant mesothelioma cell lines (ACC-Meso-1, ACC-Meso-4, EHMES-1, EHMES-10, H28, H2052 and JMN-1B), only EHMES-10 cells formed subcutaneous tumors when implanted into mice. For EHMES-10 cells, HGF facilitated invasion of the cells in collagen gel, whereas NK4 and neutralizing anti-HGF antibody suppressed the HGF-induced invasion. In addition, NK4 but not anti-HGF antibody suppressed proliferation of EHMES-10 cells in collagen, suggesting that the suppression by NK4 was independent of the HGF...

[alpha]5[beta]1 integrin antagonists reduce chemotherapy-induced premature senescence and facilitate apoptosis in human glioblastoma cells

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

The [alpha]5[beta]1 integrin represent a new therapeutic target for glioblastoma, which are malignant brain tumors difficult to cure with conventional therapies. Glioblastoma are known to be highly resistant to chemotherapy. We, therefore, investigated whether blocking [alpha]5[beta]1 integrin with specific nonpeptidic antagonists concomitantly with chemotherapy (ellipticine and temozolomide) may impact the response to chemotherapy of human glioblastoma. Here we show that inhibiting [alpha]5[beta]1 integrin with 2 selective ligands (SJ749 and K34c) decreases chemotherapy-induced premature senescence and facilitates cell apoptosis in a functional p53 background (U87MG cells). When p53 is mutated and inactive (U373 cells), chemotherapy induces p53-independent cell apoptosis instead of senesc...

Insights on distinct pathways of thiazolidinediones (PPAR[gamma] ligand)-promoted apoptosis in TRAIL-sensitive or -resistant malignant urothelial cells

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

Thiazolidinediones, including rosiglitazone and troglitazone, are insulin-sensitizing drugs and high-affinity ligands for the peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]). Apart from their antidiabetic activity, these molecules possess antitumor properties. We investigated their potential apoptotic effects on RT4 (derived from a well-differentiated Grade I papillary tumor) and T24 (derived from an undifferentiated Grade III carcinoma) bladder cancer cells. Rosiglitazone induced G2/M or G0/G1 phase cell cycle arrest in RT4 and T24 cells, respectively. Only troglitazone triggered apoptosis via extrinsic and intrinsic pathways in both cell lines. Interestingly, rosiglitazone amplified TRAIL-induced apoptosis in TRAIL-sensitive RT4 cells or let TRAIL-resistant T24 cells to ...

Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

Seventy to 40% of K-RAS wild type colorectal tumors does not seem to benefit from treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies. Recent data suggested that in presence of IGF-1 system, altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. The interaction between IGF-1 expression and K-RAS mutational analysis was tested to verify the ability of IGF-1 to identify a subgroup of patients more likely to benefit from EGFR-targeted antibodies treatment. IGF-1 expression and K-RAS mutational status was assessed in advanced colorectal cancer patients receiving irinotecan/cetuximab. One hundred twelve patients were analyzed. IGF-1 was negative in 30 patients (27%) and overexpressed in the remaining 82 cases (73%). In IGF-1 negati...

Regulation of HER expression and transactivation in human prostate cancer cells by a targeted cytotoxic bombesin analog (AN-215) and a bombesin antagonist (RC-3095)

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

Bombesin (BN) and gastrin-releasing peptide (GRP) have been shown to stimulate the growth of human prostate cancer in vivo and in vitro by mechanisms initiated by binding of the peptide to BN/GRP receptor (GRPR). GRPR is overexpressed in a variety of human cancers, including human prostatic carcinoma. This led us to evaluate the effectiveness of blocking GRPR and of chemotherapy targeted to GRPR in androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cells, which exhibit different features of disease progression. Thus, we used a cytotoxic BN/GRP analog, AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide, and a BN/GRP receptor antagonist, RC-3095. Semiquantitative RT-PCR and Western blotting revealed that mRNA and protein levels for...

Interleukins 1[alpha] and 1[beta] secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1[beta]. This effect is NF-[kappa]B and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1[beta] reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1[alpha] or IL-1[beta] secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We ...

Antitumor effects of a recombinant pseudotype baculovirus expressing Apoptin in vitro and in vivo

International Journal of Cancer — Fri, 22 Jan 2010 00:00:00 +0100

In this study, pseudotype baculovirus, a recently developed alternative gene delivery system, was used as a vector to express Apoptin. The resultant recombinant baculovirus (BV-Apoptin) efficiently expressed the Apoptin protein and induced apoptosis in HepG2 and H22 cells. Studies in vivo showed that intratumoral injection of BV-Apoptin into a xenogeneic tumor (derived from H22 murine hepatoma cells in C57BL/6 mice) significantly suppressed tumor growth, and significantly prolonged the survival of tumor-bearing mice compared to a control pseudotype baculovirus that expressed EGFP. Taken together, these results suggest that Apoptin, expressed from the pseudotype baculovirus vector, has the potential to become a therapeutic agent for the treatment of solid tumors. (Source: International Jour...

Cancer risks of hookah (shisha, narghile) tobacco use require further independent sound studies