MMI Bibliography II - Molecular Machines€¦ · We are happy to introduce to you this second...

-Bibliography Vol 2 No 1 * 2009

Special AACR*-Edition

Issue on Laser Microdissection in Cancer Proteomics

Molecular Machines & Industries

In this issue

This issue is dedicated to the 100th annual Meeting of the American Association for Cancer Research, to be held in Denver Colorado, April 18-22, 2009

Customer Reports

Cancer Proteomics by Laser Microdissection and Two-dimensional Gel Electrophoresis Comes of Age

By Tadashi Kondo MD, Phd Proteome Bioinformatics Project National Cancer Center, Tokyo, Japan

Measuring Targeted Therapeutics with Targeted Metrics: Combining the Precision of Laser Micro dissection with the Sensitivity of a Nano-immun o assay Platform for Biomarker Discovery

By David Voehringer, PhD Director Applications Cell Biosciences Inc, Palo Alto, USA

Technology & Product Features

MMI Live Cell Microdissection – The new mmi Live CellCham ber

MMI`s advanced Single Cell Isolation Concepts in Lasermicrodissection

References

The LMD-Bibliograhy is published by Molecular Machines & Industries.com, ISSN 1662-8535 Editor: Dr. Antje Plaschke-Schluetter, e-mail: [email protected] Board: Andrea Curtis, Norbert Brill, Andre Imhof & Prof. Stefan SeegerConcept & Layout: Kathrin Plaschke – Grafik & Design – HamburgThe MMI CapLift technology is a patented trademark of Molecular Machines & Industries

»Lead the way to scientifi c results«

CONTENTS

MMI-Bibliography online: www.molecular-machines.com/News

*AACR 2009 American Association for Cancer ResearchMeet the MMI Team in Denver, Colorado, booth 1020

MMI-Bibliography | 2www.molecular-machines.com

We are happy to introduce to you this second edition

of the MMI Bibliography. This issue illustrates the re-

cent advancements in Laser Microdissection, highlight-

ing the use of MMI products in this field. In particular,

Laser Microdissection combined with Proteomics for

the analysis of patient material fosters interesting pro-

tocol developments. These new protocols allow for the

discovery of new biomarkers in cancer and other dis-

eases and are a next step towards personalized medi-

cine. Tadashi Kondo intro duces a protocol for the com-

parative analysis of protein patterns in cancer versus healthy tissue. Until recently

this protocol was used to identify APC-binding protein EB1 as a novel prognostic fac-

tor in hepatocellular carcinoma. This is a breakthrough workflow for Laser Micro-

dissection to be used routinely in the clinical environment. It emphasizes the relia-

bility, robustness and user-friendliness of the MMI systems.

David Voehringer, Director Applications at CellBiosciences Inc., outlines how Laser

Microdissection in combination with CellBiosciences` Nano immunoassay reveals de-

tailed information on the phosphorylation status of critical signaling proteins.

Application of a nanoimmunoassay platform to assess changes in EGFR-dependent

signaling pathways in lung cancer cell lines: surgical resections and laser-capture

microdissection from patient-derived tumor cells exposed to EGFR tyrosine kinase

inhibitors. Mark Lloyd, Andrea W. Tu, Jiannong Li, Uyen Nguyen,

Soner Altiok, John Koomen, Lee Petruk, David W. Voehringer, Eric B. Haura.

H. Lee Moffitt Cancer Center, Tampa, FL, Cell Biosciences, Palo Alto, CA,

mmi Molecular Machines and Industries, Zurich, Switzerland

Single Cell Sorting is a strong focus at MMI and is a prerequisite for various analysis

of tumor and rare cells as introduced by Tveito et al. and Pachmann et al.

Array CGH analysis of immunomagnetically isolated breast cancer cells from sen-

tinel lymph node and bone marrow.

Siri Tveito, Leonardo A. Meza-Zepeda, Øystein Fodstad.

The Norwegian Radium Hospital, Oslo, Norway

Tracking therapy induced genetic and epigenetic heterogeneity in circulating epi the-

lial tumor cells (CETC) by single cell genome analysis: prediction of therapy success.

Pachmann, K., Camara, O., Hammer, U., Gellner, A., K.,

Rabenstein, C., Runnebaum I., B., Hoeffken.

Department of Internal Medicine, Friedrich Schiller University, Jena

The whole MMI Team hopes that you enjoy this second issue of the MMI Bibliography

and the AACR meeting 2009. Meet us and our customers at our booth # 1020 and

discover our new developments for non laser based single cell sorting.

We look forward to seeing you in Denver:

Dr. Antje Plaschke-Schluetter

MMI AG Zuerich

»Lead the way together with you«

ED ITOR IAL


Laser Microdissection is an essential tool in cancer proteomics. Tumor tissues con-

tain many cell types: tumor cells as well as non-tumor cells. Because of the mixture

of cell populations in homogenized tissue, proteome data of homogenized tissues

does not accurately represent the biological aspects of the cells of interest. In addi-

tion, sample variations will amplify the problem when heterogeneous tissue is re-

covered in the hospitals and subjected to further analysis. Thus, for accurate and re-

producible proteome studies, specific and pure cell populations should be recovered

using Laser Microdissection prior to protein extraction.

Two-dimensional gel electrophoresis is one of the most established proteomics tools.

The idea of using Laser Microdissection and two-dimensional gel electropho re sis for

cancer proteomics was published more than 10 years ago by Banks et al [1]. How-

ever, due to the limited sensitivity of spot detection methods such as silver stain ing,

Laser Microdissection was not a practical tool until recently. Craven et al reported that

in the past, it took them hours to days to recover enough cells by Laser Microdissection

for proteomic study [2]. This throughput was not acceptable in cancer proteomics

where as many tissues as possible need to be examined for conclusive results.

The solution to this situation was an ultra-high sensitive fluorescent dye to quantify

the protein samples. In 2001, Amersham Biosciences developed a not yet commer-

ci ally available fluorescent dye. The dye was designed to be 100 times more sensi-

ti ve at quantifying cystein residues of proteins than conventional silver staining. The

in ten ded use of this dye was to apply the dye for laser microdissected tissues for

can cer proteomics. After several trials, it was found that the use of the dye dramati-

cally reduced the number of laser microdissected cells needed. In 2003, this data

was published including the protocol utilizing the dye for Laser Microdissection and

two-dimensional difference gel electrophoresis (2D-DIGE) with Dr. Seike, a physi cian

working on lung cancer [3]. The dye is now commercially available from GE Health-

care Biosciences [4] (formerly Amersham Biosciences) under the name CyDye DIGE

Fluor saturation dye. For further studies, the protocol was optomized for protein an-

notation using mass spectrometry and database search. All detailed protocols are

available in a recent publication [5].

Laser Microdissection and 2D-DIGE are routine tools used in our lab. As only 1 mm2

tissue area is needed to generate several thousand protein spots in 2D-DIGE, Laser

Microdissection is now a quick and efficient method to select and collect cells. For

example, Dr. Uemura, who joined the esophageal cancer proteomics team [6], ap-

plied Laser Microdissection on 140 samples and completed his analysis in only one

month. Proteome data studied using this approach included biomarker candidates

with crucial biological backgrounds. For example, Dr. Orimo, who is a surgeon inter-

ested in malignancies of gastrointestinal tracts, recently identified APC-binding pro-

tein EB1 as a novel prognostic factor in hepatocellular carcinoma [7]. Identification of

Cancer Proteomics by Laser Microdissection and Two-dimensional Gel Electrophoresis Comes of Age

»Lead the way to cutting edge technologies«

CUSTOMER REPORTS


Tadashi Kondo, MD, PhD

Proteome Bioinformatics ProjectNational Cancer Center

Tokyo, Japan

proteins corresponding to response to treatment, metastasis and survival of patients,

and their clinical application is the research goal of cancer proteomics.

Compared to other proteomic methods, the amount of protein required for the

experiment in combination with 2D-DIGE and CyDye DIGE Fluor saturation dye is

minimal, requiring only a few µg. On the contrary, Bai et al reported that they

needed 100 µg protein from laser microdissected tissues for liver cancer proteom-

ics using cICAT (cleavable isotope-coded affinity tags, ABI, Framingham, MA), mass

spectrometry-based proteomic technology [8].

In conclusion, the combination of Laser Microdissection, two-dimensional gel elec-

trophoresis, the ultra high sensitive fluorescent dye and mass spectrometry is a high-

ly efficient and recommendable practical approach for tissue cancer proteomics [9].

References[1] Banks, R. E., Dunn, M. J., Forbes, M. A., Stanley, A., et al. | The potential use of la-ser capture microdissection to selectively obtain distinct populations of cells for proteomic analysis--preliminary findings. Electrophoresis 1999, 20, 689-700.

[2] Craven, R. A., Totty, N., Harnden, P., Selby, P. J., Banks, R. E. | Laser capture micro-dissection and two-dimensional polyacrylamide gel electrophoresis: evaluation of tissue preparation and sample limitations. Am J Pathol 2002, 160, 815-822.

[3] Kondo, T., Seike, M., Mori, Y., Fujii, K., et al. | Application of sensitive fluorescent dyes in linkage of laser microdissection and two-dimensional gel electrophoresis as a cancer proteomic study tool. Proteomics 2003, 3, 1758-1766.

[4] Shaw, J., Rowlinson, R., Nickson, J., Stone, T., et al. | Evaluation of saturation labelling two-dimensional difference gel electrophoresis fluorescent dyes. Proteomics 2003, 3, 1181-1195.

[5] Kondo, T., Hirohashi, S. | Application of highly sensitive fluorescent dyes (CyDye DIGE Fluor saturation dyes) to laser microdissection and two-dimensional differ-ence gel electrophoresis (2D-DIGE) for cancer proteomics. Nat Protoc 2006, 1, 2940-2956.

[6] Uemura, N., Nakanishi, Y., Kato, H., Saito, S., et al. | Transglutaminase 3 as a prog-nostic biomarker in esophageal cancer revealed by proteomics. Int J Cancer 2008.

[7] Orimo, T., Ojima, H., Hiraoka, N., Saito, S., et al. | Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepato-cellular carcinoma. Hepatology 2008, 48, 1851-1863.

[8] Bai, D. S., Dai, Z., Zhou, J., Liu, Y. K., et al. | Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology 2009, 49, 460-470.

[9] Kondo, T. | Tissue proteomics for cancer biomarker development: laser micro-dissection and 2D-DIGE. BMB Rep 2008, 41, 626-634.

»Lead the way to advanced proteomics«

CUSTOMER REPORTS


Sample Material for Laser Microdissection

Liver biopsy after H&E-Staining

Hematoxylin stained control picture after Laser Microdissection, collect-ed material on the cap surface

All tumor tissues from cases with well documented clinico-pathological data

Combining the Precision of Laser Microdissection with the Sensitivity of a Nano-immunoassay Platform for Biomarker DiscoveryExciting progress and tremendous efforts are being dedicated to the development

of anti-cancer therapies that target the molecular sequela that underlie carcinogen-

esis. Tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevec), have been shown

to have dramatic effects in individuals suffering from chronic myelogenous leukemia

(CLL), gastrointestinal stromal tumors (GIST) and are being evaluated in a number of

tumor types. By targeting inappropriate tyrosine kinase signaling, these compounds

trigger apoptosis resulting in decrease in tumor burden.

Since this drug development approach is predicated on the idea of targeting the mo-

lecular biology at the site of disease, novel methods are required to evaluate the

effectiveness of new therapies. Cell-based assays are often used during early phas-

es of development. However, here there is little heterogeneity and usually sufficient

material for multi-faceted evaluation. Ultimately, however, these compounds are

evaluated in the clinical setting where material is often heterogeneous and limit-

ed. Therefore, tools and/or methods that reduce heterogeneity and enable as many

endpoints as possible with this precious material are desired.

Laser capture microdissection (LCM) has proven to be an excellent tool for isolating

specific populations of cells from heterogeneous tissue structure. Specifically, differ-

ent regions of a tumor can be isolated from tissue sections (hypoxic versus non-hy-

poxic for instance) as well as micro-environment structure (normal tissue, vascula-

ture, etc…). Technologies for LCM vary and have tradeoffs for different applications.

For example collection methods of nucleic acid for amplification have been devel-

oped for most LCM tools. However, broad success of protein extraction for analysis

is limited.

The major factor influencing LCM selection is the lack of methods for amplifying pro-

tein signal. Therefore, methods for material acquisition must take into account ef-

ficiency of protein extraction and quality of extraction. These criteria limit the LCM

technologies that can be applied. Ideally, to prevent protein degradation the method

is rapid and has little impact on the protein (i.e. protein dephosphorylation or oth-

er non-biological change). We have developed a protocol using the mmi CellCut PLUS

Microdissection system (Molecular Machines & Industries) that allows for rapid isola-

tion of tissue sections as small as 500 cells. This provides sufficient material for pro-

tein evaluation in a state that maintains the phosphorylation of critical signaling pro-

teins [2]. Importantly, this method is rapidly performed on OCT embedded biopsies

under controlled conditions yet still allows downstream extraction of proteins.

In order to measure the proteins of interest, a method for analyzing small samples

of material is necessary. We employed Cell Biosciences nano-immunoassay platform

because of its ability to detect femtogram levels of protein and its unique ability to

reproducibly quantitate phosphorylation state of a protein due to changes in protein

Measuring Targeted Therapeutics with Targeted Metrics:

»Lead the way to cutting edge technologies«

CUSTOMER REPORTS


David Voehringer, PhD

Director, ApplicationsCell Biosciences Inc

Palo Alto, USA

The Hetrerogeneity of primary tumour tissue:only a percentage of material is NSCLC

A 0.8 mm core biopsy sample from Pha se II clinical trial being run at Moffitt- Cancer Center, for further details see also Lloyd et al., AACR 2009

Tumorareal

Inflammatory infiltrate

4x

40x

charge [1]. Briefly, 200 nl (or less) of sample is drawn into a 5 cm x 100 micron in-

ner-diameter capillary (400 nl total volume) along with electrophoresis reagents. An

electric field is applied and isoelectric focusing (IEF) occurs as proteins concentrate at

their net neutral charge or pI. Proteins are immobilized to the wall of the capillary

through a photoactivation capture chemistry step. Lastly, a traditional immunoassay

is performed with a primary antibody to the protein of interest (anti-total ERK in the

example provided) and HRP-conjugated reporter secondary antibody.

Due to the fact that addition of a phosphate to a protein alters a proteins charge, the

resulting data is a distribution of non-phosphorylated as well as phosphorylated iso-

forms. Area-under-the-peak measurements are extracted and total, as well as per-

cent phospho-isoform distribution of the specific protein are quantitated.

In a collaborative effort with Dr. Eric Haura and colleagues at Moffitt Cancer Center,

protein activity was measured in non-small cell lung cancer patients from both tu-

mor core biopsies collected by LCM as well as subsequent surgical resection [2].

We feel that this a

pro mising technique

that is minimally inva-

sive and could provide

a window into tumor

response to targeted

therapy. Biopsies could

be taken prior to the

initiation and through-

out the course of ther-

apy and be used as

either a prospective

technique of drug ef-

fectiveness as well as

eventually a method

to tailor therapy to an

individual patients re-

sponse [3].

References[1] O’Neill, R. A., Bhamidipati, A., Bi, X., Deb-Basu, D., Cahill, L., Ferrante, J., Gentalen, E.,

Glazer, M, Gossett, J., Hacker, K., et al. (2006) | Isoelectric focusing technology quan-tifies protein signaling in 25 cells. Proc. Natl. Acad. Sci.103:16153–16158.

[2] Haura, E. B., Lloyd, M., Tu, A. W., Li, J., Sommers, K. E., Altiok, S., Nguyen, U., Petruk, L.,

Koomen, J., Voehringer, D. W. | Application of a nano-immunoassay platform to eval-uate ERK signaling in human lung cancer specimens using less than 500 cells. (in preparation).

[3] Koomen, J. M., Haura, E. B., Bepler, G., Sutphen, R., Remily-Wood, E. R., Benson, K.,

Hussein, M., Hazlehurst, L. A., Yeatman, T. J., Hildreth, L. T., Sellers, T. A., Jacobsen, P. B.,

Fenstermacher, D. A., Dalton, W. S. | Proteomic Contributions to Personalized Cancer Care Mol. Cell. Proteomics 2008 7:1780-1794

»Lead the way to microproteomics«

CUSTOMER REPORTS


mmi CellCut PLUS

Laser Capture Microdissection of patient NCSLC biopsies

Punch biopsy from patient with NSCLC. (A) Primary tissue section prior to LCM. (B) Same section after removal of

tumor-enriched material.(C) Adjacent serial section stained

with H&E.(D) Overlay of stained and LCM serial

sections to verify section purity for tumor cells.

A

B

C

D

Read Out of a CellBiosciences NanoimmunoassayActivity of ERK isoforms varies in different patients

Introduction: The isolation and enrichment of individual live cells for culture and

differentiation experiments or for their proteomic and genomic analysis is of increas-

ing interest in stem cell research, cancer research and tissue engineering. While me-

chanical separation techniques are cumbersome, time consuming and bear the risks

of contamination or mechanical stress, faster Laser Microdissection based methods

are currently under development. The mmi CellCut PLUS in combination with the new-

ly developed mmi Live CellChamber enables contamination-free isolation of cells in

living culture.

Components of the new mmi Live CellChamber• A membrane ring, for the initial cultivation of cells

• A cell culture dish, to house the membrane ring with seeded cells

• The microdissection chamber, UV – permeable and filled with adhesive for

Laser Microdissection of single cells or group of cells.

Note: All components are sterilized and ready to use.

The Workflow Adherent cells are grown in a special metal ring on a membrane inside a petri dish.

Once a desired cell density is reached, the membrane ring is transferred to the ad-

hesive area of the microdissection chamber. The cell or cells of interest are selected

and cut using Laser Microdissection. In addition, unwanted cells can be destroyed or

ablated by using individual laser shots. The cell chamber is then removed and only

the cells of interest remain in the microdissection chamber.

Repeated selection of wanted cells: This process can be repeated using the same

metal ring in a new microdissection chamber to select and separate more than one

cell type. Once isolation is complete, sufficient medium is added to the microdissec-

tion chamber and the cells can be re-cultivated.

Your Advantage The isolation of single cells is a unique and highly useful tool in wide range of re-

search and clinical applications, including individual cell analysis, clonal expansion,

transfection experiments and stem cell research. Enzyme treatments (i.e. trypsin),

other potentially harmful selective reagents, as well as time consuming repetitive

enrichments can be avoided. The benefit is an increase in reliability, effectiveness,

and accuracy of your research.

Order this product and report back to us. Every feedback will be re warded!

Order Nr.: 50301

MMI Live Cell Microdissection – The new mmi Live CellChamber

»Lead the way to live cell microdissection«

TECHNOLOGY & PRODUCT FEATURES

Using the mmi Live CellChamber


Seed cells and cultivate to the desired cell density

Visualize your cells of interest (e.g. phase contrast, immuno labeling, etc.)

Transfer the membrane ring with cells into the mmi microdissection chamber

Selection of cells via LMD

Isolate cells by removing the membrane ringwith unwanted cells

Reculture the cells of interest and if desired, the depleted fraction

Repeat if desired

Single Cell isolation in combination with Laser Microdissection is of growing interest. Mainly, the analysis of tissue invading cells like immune cells, vascular cells, invading metastatic cells and tissue or cancer stem cells are of interest (see Fevr et al., 2007). Likewise, single cells from blood or bone marrow smears or any other aspirate can be microdissected prior to downstream analysis in cytogenetics and biomedical research.

The main advantage of Laser Microdissection over other methods, like FACS- and bead-based sorting, lies in the unsurpassed high precision and visual control of the selection and isolation process. In order to make single cell isolation reproducible and reliable, MMI established advanced concepts for single cell dissection and collection.

PTP: See what you get and get what you seePredefined Target Positioning is a new, patented product feature that allows for the pre -cise, predefined, contamination free and visually controlled collection of individual cells.

The WorkflowThe experiment to the left illustrates the collection of individual granulocytes from a blood smear. First, an overview screen of the whole sample is produced. Second, visual inspection and selection of the target cells is performed. Hint: this step can be fully au-tomated, using the mmi CellExplorer software. The UV-Cut Software is than adjusted to the PTP mode and cells (1 to ~ 100) are dissected and collected. Autodocumentation en-sures accurate in process control for the evaluation of the experiment at a later time.

Dr. Hussein et al., have successfully established single cell sorting concepts for the mo-lecular analysis of single cells in hematological diseases of myeloid origin, CML, P. Vera and others. Thus, MMI`s PTP function provides absolute reliability and visual control of the cell sorting process.

ReferencesFevr, T., Robine, S., Louvard, D., and Huelsken, J. (2007) | Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol. Cell Biol. 27, 7551-7559.

Hussein, K., Bock, O., Theophile, K., Seegers, A., Arps, H., Basten, O., Grips, K. H., Franz-Werner, J.,

Büsche, G., Kreipe, H. (2008) | Chronic myeloproliferative diseases with concurrent BCR-ABL junction and JAK2V617F mutation. Leukemia. 2008 May; 22(5): 1059-62.

Hussein, K., Dralle, W., Theophile, K., Kreipe, H., Bock, O.(2008) | Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myelo-proliferative neoplasm. Ann Hematol. 2009 Apr; 88(4): 325-32. Epub 2008 Sep 5

Hussein, K., von Neuhoff, N., Büsche, G., Buhr, T., Kreipe, H., Bock, O. | Opposite expres-sion pattern of Src kinase Lyn in acute and chronic haematological malignancies. Ann Hematol. 2009 Mar 17.

MMI’s advanced Single Cell Isolation Concepts in Laser Microdissection

»Lead the way to integrated work fl ows«

TECHNOLOGY & PRODUCT FEATURES

Settings for PTP-Collection:

Generate an overview screen of a sample, a bloodsmear is displayes here.


Adjust detailed settings for defined collection of target cells

Dissect and control col-lected cells on the ad-hesive cap

Ashida, S., Furihata, M., Katagiri, T., Tamu ra, K., Anazawa, Y., Yoshioka, H., Miki, T., Fujioka, T., Shuin, T., Naka mura, Y., and Nakagawa, H. (2006)

Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression. Clin. Cancer Res. 12, 2767-2773

Ashida, S., Nakagawa, H., Katagiri, T., Furi hata, M., Iiizumi, M., Anazawa, Y., Tsunoda, T., Takata, R., Kasahara, K., Miki, T., Fujioka, T., Shuin, T., and Nakamura, Y. (2004)

Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate can-cer: genome-wide gene-expression profiles of prostate cancers and PINs. Cancer Res. 64, 5963-5972

Bohm, M., Wieland, I., Schutze, K., and Rubben, H. (1997)

Microbeam MOMeNT: non-contact laser microdissection of membrane-mounted native tissue. Am. J. Pathol. 151, 63-67

Buckanovich, R. J., Sasaroli, D., O‘Brien-Jen kins, A., Botbyl, J., Conejo-Garcia, J. R., Benencia, F., Liotta, L. A., Gimotty, P. A., and Coukos, G. (2006)

Use of immuno-LCM to identify the in situ expression profile of cellular constituents of the tumor microenvironment. Cancer Biol. Ther. 5, 635-642

Buckanovich, R. J., Sasaroli, D., O‘Brien-Jenkins, A., Botbyl, J., Hammond, R., Katsaros, D., Sandaltzopou los, R., Liotta, L. A., Gimotty, P. A., and Coukos, G. (2007)

Tumor vascular proteins as biomarkers in ovarian cancer. J. Clin. Oncol. 25, 852-861

Cowherd, S. M., Espina, V. A., Petricoin, E. F., III, and Liotta, L. A. (2004)

Proteomic analysis of human breast cancer tissue with laser-capture microdissection and reverse-phase protein microarrays. Clin. Breast Cancer 5, 385-392

Dahl, E., Kristiansen, G., Gottlob, K., Klaman, I., Ebner, E., Hinzmann, B., Hermann, K., Pilarsky, C., Durst, M., Klinkhammer-Schalke, M., Blaszyk, H., Knuechel, R., Hartmann, A., Rosenthal, A., and Wild, P.J. (2006)

Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha2 as a potential novel prognostic marker in breast cancer. Clin. Cancer Res. 12, 3950-3960

Kasper, G., Vogel, A., Klaman, I., Grone, J., Petersen, I., Weber, B., Castanos-Velez, E., Staub, E., and Mennerich, D. (2005a)

The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression. Cancer Lett. 224, 93-103

Espina, V., Dettloff, K. A., Cowherd, S., Petricoin, E. F., III, and Liotta, L. A. (2004)

Use of proteomic analysis to monitor responses to biological therapies. Expert. Opin. Biol. Ther. 4, 83-93

Espina, V., Heiby, M., Pierobon, M., and Liotta, L. A. (2007) Laser capture microdissection technology. Expert. Rev. Mol. Diagn. 7, 647-657

Espina, V., Wulfkuhle, J. D., Calvert, V. S., VanMeter, A., Zhou, W., Coukos, G., Geho, D. H., Petricoin, E. F., III, and Liotta, L . A. (2006)

Laser-capture microdissection. Nat. Protoc. 1, 586-603

Fevr, T., Robine, S., Louvard, D., and Huelsken, J. (2007) Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol. Cell Biol. 27, 7551-7559

Gjerdrum, L. M., Abrahamsen, H. N., Villegas, B., Sorensen, B. S., Schmidt, H., and Hamilton-Dutoit, S. J. (2004)

The influence of immunohistochemistry on mRNA recovery from microdissected frozen and forma-lin-fixed, paraffin-embedded sections. Diagn. Mol. Pathol. 13, 224-233

Gjerdrum, L. M. and Hamilton-Dutoit, S. (2005a) Laser-assisted microdissection of membrane-mounted sections following immunohistochemistry and in situ hybridization. Methods Mol. Biol. 293, 139-149

Gjerdrum, L.M. and Hamilton-Dutoit, S. (2005b) Laser-assisted microdissection of membrane-mounted tissue sections. Methods Mol. Biol. 293, 127-138

Gjerdrum, L. M., Lielpetere, I., Rasmussen, L. M., Bendix, K., and Hamilton-Dutoit, S. (2001)

Laser-assisted microdissection of membrane-mounted paraffin sections for polymerase chain reaction analysis: identification of cell populations using immunohistochemistry and in situ hybridization. J. Mol. Diagn. 3, 105-110

Hatakeyama, H., Kondo, T., Fujii, K., Nakanishi, Y., Kato, H., Fukuda, S., and Hirohashi, S. (2006)

Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer. Proteomics. 6, 6300-6316

Kasper, G., Weiser, A. A., Rump, A., Sparbier, K., Dahl, E., Hartmann, A., Wild, P., Schwidetzky, U., Castanos-Velez, E., and Lehmann, K. (2005b)

Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients. Int. J. Cancer 117, 961-973

Kondo, T. and Hirohashi, S. (2006) Application of highly sensitive fluorescent dyes (CyDye DIGE Fluor saturation dyes) to laser micro-dissection and two-dimensional difference gel electrophoresis (2D-DIGE) for cancer proteomics. Nat. Protoc. 1, 2940-2956

Kondo, T., Seike, M., Mori, Y., Fujii, K., Yamada, T., and Hirohashi, S. (2003)

Application of sensitive fluorescent dyes in linkage of laser microdissection and two-dimensional gel electrophoresis as a cancer proteomic study tool. Proteomics. 3, 1758-1766

Kube, D. M., Savci-Heijink, C. D., Lamblin, A. F., Kosa ri, F., Vasmatzis, G., Cheville, J. C., Connelly, D. P., and Klee, G. G. (2007)

Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer. BMC. Mol. Biol. 8, 25

Kumar-Sinha, C., Shah, R. B., Laxman, B., Tom lins, S. A., Harwood, J., Schmitz, W., Conzelmann, E., Sanda, M.G., Wei, J. T., Rubin, M. A., and Chinnaiyan, A. M. (2004)

Elevated alpha-methylacyl-CoA racemase enzymatic activity in prostate cancer. Am. J. Pathol. 164, 787-793

»Lead the way to an easy operation«

REFERENCES


Moreno-Bueno, G., Hardisson, D., Sanchez, C.,Sarrio, D., Cassia, R., Garcia-Rostan, G., Prat, J., Guo, M., Herman, J. G., Matias-Guiu, X., Esteller, M., and Palacios, J. (2002)

Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 21, 7981-7990

Obama, K., Ura, K., Li, M., Katagiri, T., Tsunoda, T., Nomu ra, A., Satoh, S., Nakamura, Y., and Furukawa, Y. (2005)

Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepatology 41, 1339-1348

Orimo, T., Ojima, O., HIraoka, N., Saito, S., Kosuge, T., Kakisaka, T., Yokoo, H., Nakanshi, K., Karniyama, T., Todo, S., Hirohashi, S., Kondo, T. ( 2008)

Proteomic Profiling Reveals the Prognostic Value of Adenomatous Polyposis Coli-End-Binding Protein 1 in Hepatocellular Carcinoma Journal of Hepatology in press

»Lead the way toMicroscopic Manipulation«

... to be continued.

REFERENCES

Pugh, T. J., Bebb, G., Barclay, L., Sutcliffe, M., Fee, J., Salski, C., O‘Connor, R., Ho, C., Murray, N., Melosky, B., English, J., Vielkind, J., Horsman, D., Laskin, J. J. and Marra, M. A. (2007)

Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients. BMC. Cancer 7, 128

Sanchez-Aguilera, A., Delgado, J., Camacho, F. I., Sanchez-Beato, M., Sanchez, L., Montalban, C., Fres no, M. F., Martin, C., Piris, M. A., and Garcia, J. F. (2004)

Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas. Blood 103, 2351-2357

Scarpino, S., Cancellario, d. F., Di, N. A., Pasquini, A., Marzullo, A., and Ruco, L . P. (2004a)

Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid. J. Pathol. 202, 352-358

Scarpino, S., Di, N. A., Melotti, F., Talerico, C., Cancrini, A., and Ruco, L. (2007a)

Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregula-tion of VEGF-D production by tumour cells. J. Pathol. 212, 411-419

Scarpino, S., Di, N. A., Rapazzotti-Onelli, M., Pilozzi, E., and Ruco, L. (2004b)

Papillary carcinoma of the thyroid: methylation is not involved in the regulation of MET expression. Br. J. Cancer 91, 703-706

Scarpino, S., Di, N. A., Stoppacciaro, A., Anto nelli, M., Pilozzi, E., Chiarle, R., Palestro, G., Marino, M., Facciolo, F., Rendina, E. A., Webster, K. E., Kinkel, S. A., Scott, H. S., and Ruco, L. (2007b)

Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin. Exp. Immunol. 149, 504-512

Scarpino, S., Di, N. A., Taraboletti, G., Cancrini, A., and Ruco, L . P. (2005)

Hepatocyte growth factor (HGF) downregulates thrombospondin 1 (TSP-1) expression in thyroid papillary carcinoma cells. J. Pathol. 205, 50-56

Schipper, H., Papp, T., Johnen, G., Pemsel, H., Bastrop, R.,Muller, K. M., Wiethege, T., Jaworska, M., Krismann, M., Schiffmann, D., and Rahman, Q. (2003)

Mutational analysis of the nf2 tumour suppressor gene in three subtypes of primary human malignant mesotheliomas. Int. J. Oncol. 22, 1009-1017

Takata, R., Katagiri, T., Kanehira, M., Tsunoda, T., Shuin, T., Miki, T., Namiki, M., Kohri, K., Matsu shita, Y., Fujioka, T., and Nakamura, Y. (2005)

Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemo-therapy for bladder cancers through genome-wide gene expression profiling. Clin. Cancer Res. 11, 2625-2636

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Genome-wide gene expression profile analysis of esophageal squamous cell carcinomas. Int. J. Oncol. 28, 1375-1384

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The manufacturer reserves the right to make technical changes without prior notice. April 2009

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Fax : +49 89 319 048 59

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SPEC I F ICAT IONS

mmi CellCut PLUS

Item Specification

System components

Samples For all application-relevant samples (cryo or paraffin-preserved tissues,

single cells, cell compartiments, cytospins, chromosomes, etc.)

Microscopic Systems Olympus IX71 or IX81 or Nikon Eclipse

Picosecond UVa, Solid-State Laser Computer-controlled | Wavelength: 355 nm | Pulse duration: < 500 psec

Pulse energy/average energy: < 1 µjoule/appr. 4 mW | Repetition rate: > 5 kHz

mmi CapLift technology SW-controlled, covering full slides | unique, contamination-free sandwich technology

Nosepiece, UIS2 objectives 6-position nosepiece, NA and WD specified to be selected according to

application requirements | Excellent UV/IR transmission

Digital camera with ultra high sensitivity Digital colour | Digital monochrome: 1,392 x 1,040 pixels

Compact housing and FireWire connection

mmi UV-Cut software Laser energy and focus control | Full slide and Petri dish control

Inspection mode with positive target identification | Saving multi user profiles

MultiGroup function across entire sample/slides | Auto documentation for

sample, images and parameters

PC and monitor Specifications will be continuously updated according to market development

Windows XP | 19” LCD monitor

Motorised stage Computer-controlled for high-precision movement/cutting | Travelling range:

120 x 100 mm | Step width: 0.075 µm | Repositioning accuracy: 1 µm

Motorised nosepiece

Z-focus (for IX81) 10 nm step size and 1 µm reproducibility independent of movement

Direction, fine/coarse movement with 3 mm/sec max. speed

Condenser/Contrast methods BF, phase- and RC contrast and DIC, application-oriented

Fluorescence 6-cube turret, dual-level laser coupling

Options

PenScreen system operation Sensitive 21” pen screen monitor for user-friendly system operationand to

allow direct target identification with a special pen

mmi CellExplorer image analysis software Identifies and cuts out automatically defined targets based on user settings

mmi MultiCap (motorised) Allows automatic collection of targets in up to 8 different IsolationCaps

mmi MultiSlide (motorised) For microdissection of up to 3 slide assemblies

Possible CellCut system upgrade

mmi CellManipulator, optical tweezers Ultra precise, contact-free manipulation of microscopic particles

with up to 10 independent beams based on a high-quality, YAG-type infrared laser

New: mmi CellEctor A fully automated single cell sorting device

MMI Bibliography II - Molecular Machines€¦ · We are happy to introduce to you this second...

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