Neoplastic Features Research Articles

Transformation of primary human hepatocytes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Currently, there is limited knowledge of neoplastic transformation of hepatocytes in HCC. In clinical practice, the high rate of HCC local recurrence suggests the presence of different hepatocyte populations within the liver and particularly in the tumor proximity. The present study investigated primary human hepatocyte cultures obtained from liver specimens of patients affected by cirrhosis and HCC, their proliferation and transformation. Liver samples were obtained from seven HCC cirrhotic patients and from three patients with normal liver (NL). Immediately after surgery, cell outgrowth and primary cultures were obtained from the HCC lesion, the cirrhotic tissue proximal (CP, 1-3 cm) and distal (CD, >5 cm) to the margin of the neoplastic lesion, or from NL. Cells were kept in culture for 16 weeks. Morphologic analyses were performed and proliferation rate of the different cell populations compared over time. Glypican-3, Heppar1, Arginase1 and CD-44 positivity were tested. The degree of invasiveness of cells acquiring neoplastic characteristics was studied with a transwell migration assay. We observed that HCC cells maintained their morphology and unmodified neoplastic characteristics when cultured. Cells isolated from CP, showed a progressive morphologic transformation in HCC-like cells accompanied by modification of markers expression with signs of invasiveness. Absence of HCC contamination in the CP isolates was confirmed. In CD samples some of these characteristics were present and at significantly lower levels. With the present study, we are the first to have identified and describe the existence of human hepatocytes near the cancerous lesion that can transform in HCC in vitro.

Abstract PR13: miR-17-92 mediates MYC oncogene addiction

Abstract The MYC oncogene is frequently overexpressed in human cancers. MYC can transcriptionally and translationally regulate the expression of thousands of genes. However, it was unclear which specific genes are responsible for MYC to maintain a neoplastic state. The microRNA cluster miR-17-92 is a major MYC target gene known to regulate proliferation, survival, and angiogenesis, which are several of the key phenotypes associated with MYC oncogene addiction. The resemblance of biological functions between MYC and miR-17-92 thus evoked the hypothesis that miR-17-92 is causally responsible for at least part of the mechanism by which MYC maintains a neoplastic state. We have found that miR-17-92 regulates multiple histone modifiers, such as Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim, to maintain autonomous proliferation, survival, and self-renewal of MYC-driven tumors. Conversely, MYC inactivation downregulates the expression of miR-17-92 and results in the loss of neoplastic features as a consequence of restoration of senescence, apoptosis, and differentiation. Thus, the expression of miR-17-92 can dictate the cellular fates of MYC-driven tumors between survival versus apoptosis and proliferation versus senescence. Our findings provide a mechanistic insight into why tumors are dependent on or addicted to MYC. Citation Format: Yulin Li, Peter S. Choi, Stephanie C. Casey, David L. Dill, Dean W. Felsher. miR-17-92 mediates MYC oncogene addiction. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr PR13.

Evaluation of Serum Interleukin-8 (CXCL8) Concentrations in Tumor Bearing Dogs

Interleukin-8 (IL-8 or CXCL8) is a pro-inflammatory and angiogenic chemokine involved in tumorigenesis. Serum CXCL8 is elevated in various neoplastic diseases, but its potential value as a tumor marker in veterinary medicine is unknown. Here, we measured serum CXCL8 concentrations in dogs with various neoplastic diseases using a commercially available canine ELISA kit and analyzed its relationship with patient and disease features. Serum CXCL8 was detected in significantly higher concentrations in tumor bearing dogs compared with healthy patients (p<0.001). Interestingly, serum CXCL8 increased with augmenting tumor size while it decreased with raising malignancy (p=0.01 and p<0.001, respectively). We found no correlation with the tumor type, tissue origin and histological features such as vascularization, necrosis or infiltrating cells. Some of the associations between CXCL8 and neoplastic features stated in human research were corroborated in this study, suggesting the need for investigating its relevance in tumor bearing dogs.

Establishment and characterization of human lingual squamous cell carcinoma cell lines designated Nialym derived from metastatic foci of lymph node, and Nialymx derived from transplanted tumor of Nialym cells.

The squamous cell carcinoma cell lines Nialym was successfully established from metastatic foci of lymph nodes from a 48-year-old male Japanese patient with squamous cell carcinoma of the tongue. In addition, the Nialymx cell line was established from a transplanted tumor of Nialym cells in SCID mice. Nialym cells were angular, with neoplastic and pleomorphic features. Two types of Nialym cell were observed by electron microscopy; light cells and dark cells. The dark cells had a number of waved tonofilaments in the cytoplasm, while light cells showed poorly developed organelles. The population doubling times for Nialym and Nialymx cells were approximately, 46 and 42h at the 10th passage. Nialym cells secreted 4.8ng/ml VEGF and 5.9ng/ml HGF, Nialymx cells also secreted 6.7ng/ml VEGF and 4.3ng/ml HGF at the 10th passage for 3days of culture. Histopathological aspects of Nialym and Nialymx cell lines were similar. We believe that these cell lines are valuable tools for elucidating the mechanisms of cancer metastasis and developing immunotherapy and chemotherapy regimens.

Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma -HG- and Gasc for low-grade glioma -LG-) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

Correlation between semiquantitative sonoelastography and immunohistochemistry in the evaluation of testicular focal lesions.

BackgroundSonoelastography is a novel and promising imaging tool, which has been applied to breast, thyroid, and prostate tissues. The aim of this study was to evaluate focal lesions of the testes with diameters of <10 mm using sonoelastography, B-mode sonography (US), and colour Doppler ultrasonography (CDU).MethodsThirty patients who were referred to our outpatient clinics for varicocoeles, scrotal pain, scrotal enlargements, epididymitis, palpable testicular nodules, or infertility, were prospectively enrolled into this study. Ultrasound evaluations had revealed that 27 subjects had focal testicular lesions with diameters of <10 mm and 3 subjects had 10-mm spherical non-homogeneous testicular nodules. All lesions were evaluated using semiquantitative sonoelastography, and the patients underwent orchifunicolectomies. The testicular lesions were examined histopathologically. The vascularization of the lesions and the surrounding testicular parenchyma was evaluated by analysing the immunohistochemical distribution of the cluster of differentiation 31 and by calculating the vascular indices (VI). Potential associations between the strain ratios (stiffness of the lesions) and the VI were tested.ResultsAnalyses of the strain fields obtained using semiquantitative sonoelastography yielded different values for the masses and the surrounding tissues, which led to significant increases in the strain ratios. Sonoelastography upheld all of the diagnoses that were suspected when the patients were physically examined, when the serum markers were analysed, and after the patients had undergone US and CDU. Histopathological examinations confirmed the neoplastic characteristics of these masses. A significant inverse correlation was determined between the sonoelastographic strain ratio and the VI (Pearson correlation coefficient, r, = − 0.93; P < 0.001).ConclusionOur investigation shows that semiquantitative sonoelastography may provide additional objective information to support the algorithm used to diagnose testicular lesions. This might be of crucial diagnostic importance for lesions with diameters of <10 mm, particularly if they are not palpable, are negative for serum tumour markers, and if the findings from ultrasonography and CDU are equivocal. The findings from semiquantitative sonoelastography might indicate the need for surgical exploration. Further investigations with larger numbers of patients are required to corroborate these data and to support the use of semiquantitative sonoelastography in the evaluation of testicular lesions.

Abstract 1048: Dichotomy effects of Akt signaling in breast cancer

Abstract Background: The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion. Results: We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting. Conclusion: We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults. Citation Format: Huey-Jen L. Lin, Zhengang Peng. Dichotomy effects of Akt signaling in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1048. doi:10.1158/1538-7445.AM2014-1048

Can We Use Kidney Grafts With Small Neoplastic Lesions?

INTRODUCTION The widening gap between kidney transplant demand and supply prompted the expansion of selection criteria for donation to increase the available donor pool. Among donors with expanded criteria are even those with small renal cancers. We report our experience on transplantation of kidneys with small renal neoplasm. MATERIALS AND METHODS. We accidentaly found, at bench surgery time pre-transplantation, six suspected neoplastic lesions on donor kidney. All lesions were excised and histological analyzed by frozen sections. Results were confirmed in permanent sections and staged with Fuhrman nuclear grade. Following cancer diagnosis surgical excision was enlarged with achievement of free resection margins. After informed consent all grafts except one were used for transplantation. RESULTS. Histological lesions type were: three cystic renal cell carcinoma (RCC), two papillary RCC and one oncocytoma. We not utilized one of the graft with papillary RCC for the presence of multifocality. We transplanted the other five kidneys and contralateral kidney of papillary RCC. Table 1 shows donors, recipients and neoplastic characteristics. All recipients were treated with CNI based immunosuppressive regimen and at mean follow-up of 63 months (min 25, max 144) have functioning grafts and no signs of neoplastic disease. One patient died two years after transplant for cardiovascular event.Table: No Caption available.DISCUSSION. In our experience, kidneys with small tumors (T1a) can be used for transplantation. It is mandatory, in order to ensure to recipients an acceptable level of risk, carefull evaluation of histological type and grading of neoplastic disease, free resection margins and strict follow up.

Primary intestinal-type glandular lesions of the vagina: clinical, pathologic, and immunohistochemical features of 14 cases ranging from benign polyp to adenoma to adenocarcinoma.

Primary intestinal-type glandular lesions of the vagina are rare. We report a series of 14 lesions, including 1 intestinal-type polyp without neoplastic features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas. Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or endometriosis was elicited in any patient. The lesions were mostly polypoid, small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases) vagina. One carcinoma metastasized to a para-aortic lymph node; the others were confined to the vagina. The neoplasms exhibited histologic features identical to those seen in primary large intestinal tumors, including variable numbers of goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas contained areas consistent with a precursor adenoma. In 3 cases, a benign urothelium-lined duct was adjacent to the lesion, and in 2 patients benign intestinal-type epithelium was present; no other potential benign precursor lesions were seen. Immunohistochemical analysis was performed on 6 cases; the tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA-125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year, and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent literature is reviewed, and the potential origin and differential diagnosis of these lesions are discussed.

Long-term low-dose exposure of human urothelial cells to sodium arsenite activates lipocalin-2 via promoter hypomethylation

We previously reported that the sustained exposure of human urothelial cells (HUCs) to low-dose sodium arsenite induces changes in the gene expression profile and neoplastic transformation. In this study, we used the HumanMethylation27 BeadChip to analyze genome-wide methylation profiles and 5-aza-2'-deoxycytidine to examine the involvement of promoter methylation in gene expression. Because the expression of lipocalin-2 (LCN2) was highly enhanced by promoter hypomethylation in inorganic arsenic (iAs)-HUCs cells as well as bladder cancer tissues, we further showed that mutations at the binding sequences for NF-κB and C/EBP-α significantly reduced LCN2 promoter activity. By chromatin immunoprecipitation assay, we demonstrated the significantly increased binding of RelA (p65) and NF-κB1 (p50) to the hypomethylated promoter of LCN2 in the iAs-HUCs. Furthermore, we also demonstrated that LCN2 overexpression was crucial for the neoplastic characteristics of the iAs-HUCs, such as enhanced anchorage-independent growth, resistance to serum deprivation and activation of NF-κB signaling. In addition, our results indicated that enhanced NF-κB activity in iAs-HUCs was via LCN2-mediated increase in intracellular iron and reactive oxygen species levels. Taken together, our results show that sustained low-dose arsenic exposure results in epigenetic changes and enhanced oncogenic potential via LCN2 overexpression.

Induction of neoplastic cells in rat skin

To investigate the induction of neoplastic lesions under the action of ultraviolet B radiation (UVR-B) and dimethyl benzanthracene (DMBA). Forty Wistar rats were assigned to four groups (ten animals each), according to the procedure: group A received UVR-B irradiation, group B received topic DMBA, group C, UVR-B+DMBA and group D as control, observed for ten weeks. In the tenth week they went through a skin biopsy and histopathological study. The average thickness of the epidermis was calculated and evaluated statistically. Macroscopic lesions in group B were more of inflammatory kind compared to group A. Group C presented more injuries with neoplastic features than the others (p<0.01). Histologically there was a significant increase in thickness of the epidermis of all groups compared to control, however the greatest thickness measures occurred in Group C (p<0.01). The population exposed to ultraviolet B radiation is subject to suffer skin lesions that can develop into cancer. The association with hydrocarbons as the dimethyl benzanthracene increases the possibility of malignancy. May not be clinically evident determine when a solar keratosis ends and when a CEC begins. For this reason, histological study associated with health education prompting the early and irreversible injury prevention is necessary.

Cystic and micropapillary epithelial changes of peribiliary glands might represent a precursor lesion of biliary epithelial neoplasms

A tumorigenic role of peribiliary glands (PBGs) has been suggested recently. This study was performed to clarify the histological characteristics of PBGs showing cystic and micropapillary epithelial changes. From histological sections of a total of 938 autopsy livers, cases with cystic and micropapillary changes of the epithelial cells of intrahepatic PBGs were collected. PBGs with cystic change that lacked micropapillary epithelial changes were referred to as cystic lesion. Mucin staining and immunohistochemical analysis were performed, and the results were compared between cystic and micropapillary (C-P) lesions and cystic lesions. C-P and cystic lesions were observed in 9 (1%) and 40 (4%) , respectively. The atypia of micropapillary epithelium was usually mild, but in a single case, invasive adenocarcinoma accompanied a C-P lesion. Abundant mucin expression was observed in all cases of C-P lesion, which was similar to mucinous acini of normal PBGs rather than serous acini. Immunohistochemical analysis showed that MUC5AC was more frequently expressed in C-P lesions than in cystic lesions. Immunohistochemical expression of cyclin D1 and S100P was characteristically found in C-P lesions. Mean Ki-67 labeling index of C-P lesions was significantly higher than that of cystic lesions. The immunoprofile of C-P lesions was similar to that of the branch-type intraductal papillary mucinous neoplasm of the pancreas. These results suggest that C-P lesions may have neoplastic features and might represent a precursor of biliary epithelial neoplasms, including branch-type intraductal papillary neoplasm of the bile duct as well as mucin-producing cholangiocarcinoma, a concept that we have recently proposed.

Early results of a trimodality treatment for superior sulcus tumors.

IntroductionSuperior sulcus tumors are a unique form of lung cancer. Preoperative concurrent radio- and chemotherapy improves the results of treating these lung tumors.AimThe study aimed to assess the early results of a trimodality treatment for superior sulcus tumors.Material and methodsFifty-six superior sulcus tumors patients were operated on between 2006 and 2013. Data from 25 patients undergoing preoperative chemoradiotherapy were analyzed. Fifteen men and 10 women were treated (mean age: 59 years). All patients experienced pain in the pectoral girdle of the chest.ResultsNineteen patients received preoperative chemoradiotherapy consisting of 2 chemotherapy cycles with cisplatin (a different number of cycles was administered in 6 cases) and irradiation at a mean dose of 51.2 Gy (30-60 Gy) in 25 fractions (25-30 fractions). All patients underwent upper lobectomy. Twenty-two patients underwent chest wall resection, whereas 3 patients underwent extrapleural excision of the infiltrate without rib resection. Stages IIB and IIIB were diagnosed in 15 and 10 patients, respectively. In 9 samples, no neoplastic features were found, 9 showed individual neoplastic lesions, and in 7 most tumor cells were necrotized. The R1 resection was noted in 2 patients. Mean hospitalization time was 13 days. No perioperative deaths were noted.ConclusionsThe trimodality treatment for superior sulcus tumors is a safe method. Perioperative mortality and the number of complications observed among patients treated with this method are similar to those observed in one-phase surgery. In over half of the patients, chemoradiotherapy resulted in complete or nearly complete remission of the neoplasm.

Regulation of tumor growth and metastasis: the role of tumor microenvironment.

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body’s immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor’s surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

Nonossifying Fibroma of Rib

Nonossifying fibroma is usually an asymptomatic benign lesion seen in the first 2 decades of life, occurring commonly in the long bones of lower extremities. Biopsy is required for symptomatic lesions and for those that develop in unusual sites and outside the usual age of presentation [1]. Histologically, there are no neoplastic features. It is considered to be a developmental bony defect that is usually self-limiting, with spontaneous resolution [2].

Meta‐analysis of expression of l(3)mbt tumor‐associated germline genes supports the model that a soma‐to‐germline transition is a hallmark of human cancers

Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential.

Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract

Endomicroscopy allows in vivo microscopic investigation of enteral mucosa during endoscopic examinations. The aim of this study was to determine interobserver variability in the evaluation of endomicroscopic pictures of several organs by groups of investigators composed of confocal experts, pathologists and students. Twenty-five selected representative endomicroscopic pictures of the colon, stomach and oesophagus (total number, 75) were evaluated based on tissue, inflammatory and neoplastic changes (secondary endpoints). The endomicroscopic presence of neoplastic features was the primary endpoint and correlated with the final histological diagnosis. The kappa values for experts examining colon, stomach, and oesophagus pictures were 0.80, 0.91, and 0.488, respectively; for students 0.74, 0.684, and 0.527 and for pathologists 0.749, 0.633, and 0.346, respectively. Neoplasia was accurately diagnosed in 67-97% of patients with no significant differences between the 3 groups. Tissue differentiation was determined best by pathologists, whereas the degree of inflammation was better diagnosed by experts and students. In all 3 groups the diagnosis of oesophageal diseases was the most difficult. Endomicroscopic images can be interpreted with high concordance. In our study, the diagnostic reliability was not different between students, endomicroscopic experts, and pathologists. Thus, endomicroscopy could be an additional and reliable imaging modality for diagnosing mucosal neoplasia of the gut.

Abstract A27: Proteomic study of the of posttranslational modifications (phosphorylation and glycosylation) and its significance in human breast cancer.

Abstract Post translational modifications are the biochemical modifications introduced into the protein after translation (or during translation in case of co-translational modification). Various changes that occur are in the form of chemical groups added to various residues of the target protein by specific enzymes like glycosyltransferase, kinase, methyltransferase, etc. Various studies have shown that cancer cells differ from non-neoplastic cells not only in expression of proteins and their related function, but they also have major differences in the pattern of post-translational modification. These changes may be direct result of difference in expression levels of PTM-responsible enzymes, or differences in the functioning of the same. In the same manner, differences in PTM pattern of cancer proteins leads to many structural and functional changes in the target proteins, many of which may be responsible in furthering the neoplastic characteristics and survival of the cancer cell. Since PTM leads to change in functionality in target proteins, this study aims to find a direct relation between change in function of both pro-apoptotic and anti-apoptotic proteins and cancer cell immortality. Theoretically, pro-apoptotic proteins need to be non-functional for the cell to skip apoptosis, as is often seen in cancer cells. Also, the activity of anti-apoptotic proteins needs to be subdued by PTM to reach the same results. Differential PTM of various proteins in cancer cells with respect to non-neoplastic cells has been seen to be of great significance. This upregulation or downregulation of certain type of specific PTM can be a factor for the overall progression and development of cancer. Present study was desined with an aim to identifying the proteome exclusive to breast cancer cells, and also to study the differential PTM pattern of the same and determine the significance of this difference in various aspects of cancer occurrence, pathogenesis and progression. We found that the there is a significant change in the expression profiling of phosphorylation and glycosylation patterns of various proteins associated with breast cancer as assessed by using various bioinformatic based tools. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A27. Citation Format: Navkiran Kaur, Parul Jauhari. Proteomic study of the of posttranslational modifications (phosphorylation and glycosylation) and its significance in human breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A27.

Rabaptin-5 and Rabex-5 are neoplastic tumour suppressor genes that interact to modulate Rab5 dynamics in Drosophila melanogaster

Endocytosis plays an important role in the regulation of tumour growth and metastasis. In Drosophila, a number of endocytic neoplastic tumour suppressor genes have been identified that when mutated cause epithelial disruption and over-proliferation. Here we characterise the Drosophila homologue of the Rab5 effector Rabaptin-5, and show that it is a novel neoplastic tumour suppressor. Its ability to bind Rab5 and modulate early endosomal dynamics is conserved in Drosophila, as is its interaction with the Rab5 GEF Rabex5, for which we also demonstrate neoplastic tumour suppressor characteristics. Surprisingly, we do not observe disruption of apico-basal polarity in Rabaptin-5 and Rabex-5 mutant tissues; instead the tumour phenotype is associated with upregulation of Jun N-terminal Kinase (JNK) and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signalling.

Knitwear Design of Domino-knitting Stitch Using Mondrian's Neo Plastic Characteristics

Knitwear Design of Domino-knitting Stitch Using Mondrian's Neo Plastic Characteristics