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Article ; Online: Simplifying stable CHO cell line generation with high probability of monoclonality by using microfluidic dispensing as an alternative to fluorescence activated cell sorting.

Chakrabarti, Lina / Savery, James / Mpindi, John Patrick / Klover, Judith / Li, Lina / Zhu, Jie

2024 , Page(s) e3441

Abstract: Single cell cloning is a critical step for cell line development (CLD) for therapeutic protein production, with proof of monoclonality being compulsorily sought in regulatory filings. Among the different single cell deposition technologies, we found that ...

Abstract	Single cell cloning is a critical step for cell line development (CLD) for therapeutic protein production, with proof of monoclonality being compulsorily sought in regulatory filings. Among the different single cell deposition technologies, we found that fluorescence activated cell sorting (FACS) offers high probability of monoclonality and can allow selective enrichment of the producer cells. However, FACS instruments are expensive and resource-intensive, have a large footprint, require highly skilled operators and take hours for setup, thereby complicating the cell line generation process. With the aim of finding an easy-to-use alternative to FACS, we identified a flow cytometry-based microfluidic cell dispenser, which presents a single cell sorting solution for biopharmaceutical CLD. The microfluidic cell dispenser is small, budget-friendly, easy-to-use, requires lower-cost consumables, permits flow cytometry-enabled multiparametric target cell enrichment and offers fast and gentle single cell dispensing into multiwell plates. Following comprehensive evaluation, we found that single cell deposition by the microfluidic cell dispenser resulted in >99% probability of monoclonality for production cell lines. Moreover, the clonally derived producer cell lines generated from the microfluidic cell dispenser demonstrated comparable or improved growth profiles and production capability compared to the FACS derived cell lines. Taken together, microfluidic cell dispensing can serve as a cost-effective, efficient and convenient alternative to FACS, simplifying the biopharmaceutical CLD platform with significant reductions in both scientist time and running costs.
Language	English
Publishing date	2024-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	165657-0
ISSN	1520-6033 ; 8756-7938
ISSN (online)	1520-6033
ISSN	8756-7938
DOI	10.1002/btpr.3441
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Article ; Online: Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours.

Pulkka, Olli-Pekka / Mpindi, John-Patrick / Tynninen, Olli / Nilsson, Bengt / Kallioniemi, Olli / Sihto, Harri / Joensuu, Heikki

Journal of cellular and molecular medicine

2018 Volume 22, Issue 4, Page(s) 2220–2230

Abstract: The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST ... ...

Abstract	The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/metabolism ; Gastrointestinal Stromal Tumors/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Integrin alpha4/genetics ; Integrin alpha4/metabolism ; Male ; Middle Aged ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-kit/metabolism
Chemical Substances	Integrin alpha4 (143198-26-9) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2018-01-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.13502
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Article ; Online: Breeze: an integrated quality control and data analysis application for high-throughput drug screening.

Potdar, Swapnil / Ianevski, Aleksandr / Mpindi, John-Patrick / Bychkov, Dmitrii / Fiere, Clément / Ianevski, Philipp / Yadav, Bhagwan / Wennerberg, Krister / Aittokallio, Tero / Kallioniemi, Olli / Saarela, Jani / Östling, Päivi

Bioinformatics (Oxford, England)

2020 Volume 36, Issue 11, Page(s) 3602–3604

Abstract: Summary: High-throughput screening (HTS) enables systematic testing of thousands of chemical compounds for potential use as investigational and therapeutic agents. HTS experiments are often conducted in multi-well plates that inherently bear technical ... ...

Abstract	Summary: High-throughput screening (HTS) enables systematic testing of thousands of chemical compounds for potential use as investigational and therapeutic agents. HTS experiments are often conducted in multi-well plates that inherently bear technical and experimental sources of error. Thus, HTS data processing requires the use of robust quality control procedures before analysis and interpretation. Here, we have implemented an open-source analysis application, Breeze, an integrated quality control and data analysis application for HTS data. Furthermore, Breeze enables a reliable way to identify individual drug sensitivity and resistance patterns in cell lines or patient-derived samples for functional precision medicine applications. The Breeze application provides a complete solution for data quality assessment, dose-response curve fitting and quantification of the drug responses along with interactive visualization of the results. Availability and implementation: The Breeze application with video tutorial and technical documentation is accessible at https://breeze.fimm.fi; the R source code is publicly available at https://github.com/potdarswapnil/Breeze under GNU General Public License v3.0. Contact: swapnil.potdar@helsinki.fi. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Data Analysis ; Drug Evaluation, Preclinical ; Humans ; Quality Control ; Software
Language	English
Publishing date	2020-03-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btaa138
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Article: High miR-30 Expression Associates with Improved Breast Cancer Patient Survival and Treatment Outcome.

Jamshidi, Maral / Fagerholm, Rainer / Muranen, Taru A / Kaur, Sippy / Potdar, Swapnil / Khan, Sofia / Netti, Eliisa / Mpindi, John-Patrick / Yadav, Bhagwan / Kiiski, Johanna I / Aittomäki, Kristiina / Heikkilä, Päivi / Saarela, Jani / Bützow, Ralf / Blomqvist, Carl / Nevanlinna, Heli

Cancers

2021 Volume 13, Issue 12

Abstract: Deregulated miRNA expression has been suggested in several stages of breast cancer pathogenesis. We have studied the miR-30 family, in particular miR-30d, in relation to breast cancer patient survival and treatment outcomes. With tumor specimens from ... ...

Abstract	Deregulated miRNA expression has been suggested in several stages of breast cancer pathogenesis. We have studied the miR-30 family, in particular miR-30d, in relation to breast cancer patient survival and treatment outcomes. With tumor specimens from 1238 breast cancer patients, we analyzed the association of miR-30d expression with tumor characteristics with the 5-year occurrence of breast cancer-specific death or distant metastasis (BDDM), and with 10-year breast cancer survival (BCS). We conducted a two-stage drug-screen to investigate the impact of miR-30 family members (miR-30a-30e) on sensitivity to doxorubicin and lapatinib in six breast cancer cell lines HCC1937, HCC1954, MDA-MB-361, MCF7, MDA-MB-436 and CAL-120, using drug sensitivity scores (DSS) to compare the miR-30 family mimics to their specific inhibitors. The study was complemented with Ingenuity Pathway Analysis (IPA) with the METABRIC data. We found that while high miR-30d expression is typical for aggressive tumors, it predicts better metastasis-free (
Language	English
Publishing date	2021-06-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13122907
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Article ; Online: Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

Kangaspeska, Sara / Hultsch, Susanne / Jaiswal, Alok / Edgren, Henrik / Mpindi, John-Patrick / Eldfors, Samuli / Brück, Oscar / Aittokallio, Tero / Kallioniemi, Olli

BMC cancer

2016 Volume 16, Page(s) 378

Abstract: Background: The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo ... ...

Abstract	Background: The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Methods: Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. Results: We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. Conclusion: This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.
MeSH term(s)	Breast Neoplasms/genetics ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Drugs, Investigational ; Exome ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Regulatory Networks/drug effects ; Genomic Instability ; High-Throughput Screening Assays/methods ; Humans ; Imidazoles/pharmacology ; MCF-7 Cells ; Naphthoquinones/pharmacology ; Paclitaxel/pharmacology ; Sequence Analysis, DNA/methods ; Small Molecule Libraries/pharmacology ; Tamoxifen/pharmacology
Chemical Substances	Drugs, Investigational ; Imidazoles ; Naphthoquinones ; Small Molecule Libraries ; Tamoxifen (094ZI81Y45) ; Paclitaxel (P88XT4IS4D) ; sepantronium (UZ77T1VFBM)
Language	English
Publishing date	2016-07-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-016-2452-5
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Article ; Online: Consistency in drug response profiling.

Mpindi, John Patrick / Yadav, Bhagwan / Östling, Päivi / Gautam, Prson / Malani, Disha / Murumägi, Astrid / Hirasawa, Akira / Kangaspeska, Sara / Wennerberg, Krister / Kallioniemi, Olli / Aittokallio, Tero

Nature

2016 Volume 540, Issue 7631, Page(s) E5–E6

Language	English
Publishing date	2016--30
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature20171
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.

Mpindi, John-Patrick / Swapnil, Potdar / Dmitrii, Bychkov / Jani, Saarela / Saeed, Khalid / Wennerberg, Krister / Aittokallio, Tero / Östling, Päivi / Kallioniemi, Olli

Bioinformatics (Oxford, England)

2015 Volume 31, Issue 23, Page(s) 3815–3821

Abstract: ... for generating accurate dose-response curves.: Contact: john.mpindi@helsinki.fi.: Availability and ...

Abstract	Motivation: Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. Results: We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. Contact: john.mpindi@helsinki.fi. Availability and implementation: Supplementary information: R code and Supplementary data are available at Bioinformatics online.
MeSH term(s)	Algorithms ; Antineoplastic Agents/pharmacology ; Data Interpretation, Statistical ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays/methods ; Humans ; Male ; Normal Distribution ; Prostatic Neoplasms/drug therapy ; Tumor Cells, Cultured
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2015-12-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv455
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Article: Anagrelide for Gastrointestinal Stromal Tumor.

Clinical cancer research : an official journal of the American Association for Cancer Research

2018 Volume 25, Issue 5, Page(s) 1676–1687

Abstract: Purpose: Gastrointestinal stromal tumor (GIST) is a common type of soft-tissue sarcoma. Imatinib, an inhibitor of KIT, platelet-derived growth factor receptor alpha (PDGFRA), and a few other tyrosine kinases, is highly effective for GIST, but advanced ... ...

Abstract	Purpose: Gastrointestinal stromal tumor (GIST) is a common type of soft-tissue sarcoma. Imatinib, an inhibitor of KIT, platelet-derived growth factor receptor alpha (PDGFRA), and a few other tyrosine kinases, is highly effective for GIST, but advanced GISTs frequently progress on imatinib and other approved tyrosine kinase inhibitors. We investigated phosphodiesterase 3 (PDE3) as a potential therapeutic target in GIST cell lines and xenograft models. Experimental design: The GIST gene expression profile was interrogated in the MediSapiens IST Online transcriptome database comprising human tissue and cancer samples, and PDE3A and PDE3B expression was studied using IHC on tissue microarrays (TMA) consisting of 630 formalin-fixed human tissue samples. GIST cell lines were screened for sensitivity to 217 anticancer compounds, and the efficacy of PDE inhibitors on GIST was further studied in GIST cell lines and patient-derived mouse xenograft models. Results: GISTs expressed PDE3A and PDE3B frequently compared with other human normal or cancerous tissues both in the Conclusions: PDE3A and PDE3B are frequently expressed in GIST. Anagrelide had anticancer efficacy in GIST xenograft models and warrants further testing in clinical trials.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cell Survival/drug effects ; Cyclic Nucleotide Phosphodiesterases, Type 3/genetics ; Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Gastrointestinal Stromal Tumors/drug therapy ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/mortality ; Gastrointestinal Stromal Tumors/pathology ; High-Throughput Screening Assays ; Humans ; Mice ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Quinazolines/pharmacology ; Quinazolines/therapeutic use ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Platelet Aggregation Inhibitors ; Quinazolines ; Cyclic Nucleotide Phosphodiesterases, Type 3 (EC 3.1.4.17) ; anagrelide (K9X45X0051)
Language	English
Publishing date	2018-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-18-0815
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Article ; Online: A functional genetic screen reveals new regulators of β1-integrin activity.

Pellinen, Teijo / Rantala, Juha K / Arjonen, Antti / Mpindi, John-Patrick / Kallioniemi, Olli / Ivaska, Johanna

Journal of cell science

2012 Volume 125, Issue Pt 3, Page(s) 649–661

Abstract: β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and ... ...

Abstract	β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of β1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of β1 integrin activity. Cell biological analysis of the identified β1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates β1 integrins and that both proteins associate with β1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of β1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.
MeSH term(s)	Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation ; Genetic Testing/methods ; Humans ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Male ; Matrix Metalloproteinase 8/genetics ; Matrix Metalloproteinase 8/metabolism ; Microarray Analysis ; Neoplasm Invasiveness/genetics ; Neoplasm Invasiveness/physiopathology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; RNA Interference ; Tetraspanin 29/genetics ; Tetraspanin 29/metabolism
Chemical Substances	CD9 protein, human ; Integrin beta1 ; Tetraspanin 29 ; MMP8 protein, human (EC 3.4.24.34) ; Matrix Metalloproteinase 8 (EC 3.4.24.34)
Language	English
Publishing date	2012-02-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.090704
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Article ; Online: REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

Lehtinen, Laura / Vesterkvist, Pia / Roering, Pia / Korpela, Taina / Hattara, Liisa / Kaipio, Katja / Mpindi, John-Patrick / Hynninen, Johanna / Auranen, Annika / Davidson, Ben / Haglund, Caj / Iljin, Kristiina / Grenman, Seija / Siitari, Harri / Carpen, Olli

PloS one

2016 Volume 11, Issue 3, Page(s) e0151590

Abstract: Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The ... ...

Abstract	Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.
MeSH term(s)	Adenocarcinoma, Mucinous/blood ; Adenocarcinoma, Mucinous/metabolism ; Adenocarcinoma, Mucinous/pathology ; Biomarkers, Tumor/metabolism ; CA-125 Antigen/blood ; Databases, Factual ; Female ; Humans ; Lectins, C-Type/blood ; Lectins, C-Type/metabolism ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Pancreatitis-Associated Proteins ; Proteins/metabolism
Chemical Substances	Biomarkers, Tumor ; CA-125 Antigen ; Lectins, C-Type ; Pancreatitis-Associated Proteins ; Proteins ; REG4 protein, human ; WFDC2 protein, human
Language	English
Publishing date	2016-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0151590
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