LIVIVO - Search results -

Search results

Result 1 - 10 of total 221

Search options

Article: Surgery for pleural mesothelioma, when it is indicated and why: arguments against surgery for malignant pleural mesothelioma.

Woodard, Gavitt A / Jablons, David M

2020 Volume 9, Issue Suppl 1, Page(s) S86–S91

Abstract: Extrapleural pneumonectomy (EPP) and pleurectomy decortication (PD) are radical operations for malignant pleural mesothelioma (MPM) that remain controversial among thoracic surgeons. There is a lack of randomized evidence to support a survival benefit ... ...

Abstract	Extrapleural pneumonectomy (EPP) and pleurectomy decortication (PD) are radical operations for malignant pleural mesothelioma (MPM) that remain controversial among thoracic surgeons. There is a lack of randomized evidence to support a survival benefit when major surgical resection is included in multi-modality treatment regimens. Current data from retrospective single institution reviews and prospective trials such as the Surgery for Mesothelioma After Radiation Therapy (SMART) trial are limited by biased patient selection to include only the healthiest patients with most limited disease burden. This patient population predictably has relatively longer survival times than patients with inoperable advanced disease. The only randomized trial to date that has objectively evaluated the true benefit of surgical resection was the Mesothelioma and Radical Surgery (MARS) trial which actually showed shorter survival times among patients who underwent EPP compared with those treated medically. Critics of the MARS trial cite a high perioperative mortality rate for driving these results, however a similar trial has never been repeated to refute the MARS trial results. Finally, it is relevant to consider the high mortality and morbidity rates associated with major operations when recommending these interventions to MPM patients. There is a growing body of literature that identifies patients who clearly obtain no benefit from surgery including those with sarcomatoid or biphasic histology, nodal disease, elevated CRP, elevated platelets and advanced age. Surgery in MPM has risks and is of questionable benefit with outcomes data biased by patient selection of those who will have longer overall survival times regardless of treatment.
Language	English
Publishing date	2020-02-13
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr.2020.01.08
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- Full text online
- Order with fees

Article ; Online: Extracellular sulfatases as potential blood-based biomarkers for early detection of lung cancer.

Yang, Yi-Wei / Jablons, David M / Lemjabbar-Alaoui, Hassan

Experimental lung research

2021 Volume 47, Issue 6, Page(s) 261–279

Abstract: Purpose: Non-small lung (NSCLC) is the deadliest cancer, with survival measured in months. Earlier diagnosis using a robust biomarker would likely improve survival. This study aims to determine whether blood levels of the extracellular sulfatases (SULF1 ...

Abstract	Purpose: Non-small lung (NSCLC) is the deadliest cancer, with survival measured in months. Earlier diagnosis using a robust biomarker would likely improve survival. This study aims to determine whether blood levels of the extracellular sulfatases (SULF1 and SULF2) and their bio-activity can serve as novel biomarkers for NSCLC early detection. Materials and methods: Using human plasma specimens from NSCLC patients, nonmalignant COPD patients, and healthy individuals, we determined the association between plasma SULF levels and the presence of NSCLC. We assessed the plasma SULF levels as a function of sex and age. We also evaluated the plasma levels of heparin-binding factors potentially mobilized by the SULFs. To increase test specificity of blood SULF2 as a biomarker for the early diagnosis of NSCLC, we investigated the presence of a tumor-specific SULF2 isoform released in the blood, which could be used as a biomarker alone or in multiplex assays. Results: The median level of plasma SULF2 was significantly elevated in NSCLC patients than in healthy controls (∼2 fold). However, these data were confounded by age. Surprisingly, COPD patients also showed a dramatically increased SULF2 plasma level. We showed a significant increase in the median plasma levels of several HSPG-binding factors in early-stage NSCLC patients compared to controls. Furthermore, we revealed a significant positive correlation of the SULF2 protein level with the plasma levels of two HSPG-binding factors IL6 and IL8. We demonstrated that NSCLC cancer cells and tissues overexpress a SULF2 splice variant. We determined the presence of a SULF2 splice variant form in NSCLC plasma, which was not detectable in COPD and control plasmas. Conclusion: Our findings highlight the potential for the plasma levels of SULF2 protein and its bio-activity as novel blood biomarkers for early diagnosis of NSCLC.
MeSH term(s)	Biomarkers/blood ; Early Detection of Cancer ; Humans ; Lung Neoplasms/diagnosis ; Sulfatases/blood
Chemical Substances	Biomarkers ; SULF2 protein, human (EC 3.1.6.-) ; Sulfatases (EC 3.1.6.-)
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603791-4
ISSN	1521-0499 ; 0190-2148
ISSN (online)	1521-0499
ISSN	0190-2148
DOI	10.1080/01902148.2021.1885525
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1568: 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)

Order via subito

Details ▾

Article: Novel dual action PARP and microtubule polymerization inhibitor AMXI-5001 powerfully inhibits growth of esophageal carcinoma both alone and in combination with radiotherapy.

Brand, Nathan R / Yang, Yi-Wei / Ding, Vivianne / Dutta, Hannah / Peto, Csaba J / Lemjabbar-Alaoui, Hassan / Jablons, David M

American journal of cancer research

2024 Volume 14, Issue 1, Page(s) 378–389

Abstract: Esophageal cancer is one of the leading causes of cancer deaths globally with an incidence that is concentrated in specific hot spots in Eastern Asia, the Middle East, Eastern Africa, and South America. 10-year overall survival for patients treated with ... ...

Abstract	Esophageal cancer is one of the leading causes of cancer deaths globally with an incidence that is concentrated in specific hot spots in Eastern Asia, the Middle East, Eastern Africa, and South America. 10-year overall survival for patients treated with standard of care chemoradiation followed by surgical resection is below 40% highlighting the need for novel therapeutics to treat this disease. We assessed the effect of AMXI-5001, a novel small molecule poly ADP-Ribose polymerase (PARP) inhibitor and microtubule polymerization inhibitor on tumor growth inhibition in both
Language	English
Publishing date	2024-01-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models.

Li, P Jonathan / Roose, Jeroen P / Jablons, David M / Kratz, Johannes R

Cancers

2021 Volume 13, Issue 4

Abstract: 3D models of cancer have the potential to improve basic, translational, and clinical studies. Patient-derived xenografts, spheroids, and organoids are broad categories of 3D models of cancer, and to date, these 3D models of cancer have been established ... ...

Abstract	3D models of cancer have the potential to improve basic, translational, and clinical studies. Patient-derived xenografts, spheroids, and organoids are broad categories of 3D models of cancer, and to date, these 3D models of cancer have been established for a variety of cancer types. In lung cancer, for example, 3D models offer a promising new avenue to gain novel insights into lung tumor biology and improve outcomes for patients afflicted with the number one cancer killer worldwide. However, the adoption and utility of these 3D models of cancer vary, and demonstrating the fidelity of these models is a critical first step before seeking meaningful applications. Here, we review use cases of current 3D lung cancer models and bioinformatic approaches to assessing model fidelity. Bioinformatics approaches play a key role in both validating 3D lung cancer models and high dimensional functional analyses to support downstream applications.
Language	English
Publishing date	2021-02-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13040701
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.

Lee, Jen-Chieh / Liu, Shu / Wang, Yucheng / Liang, You / Jablons, David M

Oncotarget

2022 Volume 13, Page(s) 1217–1236

Abstract: Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. ... ...

Abstract	Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. We sought to examine the anticancer effect of MK256 on AML. In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation. Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.
MeSH term(s)	Humans ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase 8/antagonists & inhibitors ; Down-Regulation ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; STAT Transcription Factors/genetics ; Animals
Chemical Substances	CDK8 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 8 (EC 2.7.11.22) ; Protein Kinase Inhibitors ; STAT Transcription Factors
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.28305
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Comparative genomics between matched solid and lepidic portions of semi-solid lung adenocarcinomas.

Woodard, Gavitt A / Ding, Vivianne / Cho, Christina / Brand, Nathan R / Kratz, Johannes R / Jones, Kirk D / Jablons, David M

Lung cancer (Amsterdam, Netherlands)

2023 Volume 180, Page(s) 107211

Abstract: Background: Genetic changes that drive the transition from lepidic to invasive cancer development within a radiographic ground glass or semi-solid lung lesion (SSL) are not well understood. Biomarkers to predict the transition to solid, invasive cancer ... ...

Abstract	Background: Genetic changes that drive the transition from lepidic to invasive cancer development within a radiographic ground glass or semi-solid lung lesion (SSL) are not well understood. Biomarkers to predict the transition to solid, invasive cancer within SSL are needed. Methods: Patients with surgically resected SSL were identified retrospectively from a surgical database. Clinical characteristics and survival were compared between stage I SSL (n = 65) and solid adenocarcinomas (n = 120) resected during the same time period. Areas of normal lung, in situ lepidic, and invasive solid tumor were microdissected from within the same SSL specimens and next generation sequencing (NGS) and Affymetrix microarray of gene expression were performed. Results: There were more never smokers, Asian patients, and sub-lobar resections among SSL but no difference in 5-year survival between SSL and solid adenocarcinoma. Driver mutations found in both lepidic and solid invasive portion were EGFR (43%), KRAS (21%), and DNMT3A (5%). CEACAM5 was the most upregulated gene found in solid, invasive portions of SSL. Lepidic and invasive solid areas had many similarities in gene expression, however there were some significant differences with the gene SPP1 being a unique biomarker for the invasive component of a SSL. Conclusions: Common lung cancer driver mutations are present in in situ lepidic as well as invasive solid portions of a SSL, suggesting early development of driver mutations. CEACAM5 and SPP1 emerged as promising biomarkers of invasive potential in semi-solid lesions. Other studies have shown both genes to correlate with poor prognosis in lung cancer and their role in evolution of semi-solid lung lesions warrants further study.
MeSH term(s)	Humans ; Lung Neoplasms/pathology ; Retrospective Studies ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma/pathology ; Genomics
Language	English
Publishing date	2023-04-21
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2023.107211
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2135: 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)
Zs.MO 423: Show issues

Order via subito

Details ▾

Article: The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC).

Hsu, Ping-Chih / Yang, Cheng-Ta / Jablons, David M / You, Liang

Cancers

2020 Volume 12, Issue 6

Abstract: The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter ... ...

Abstract	The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src-YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.
Language	English
Publishing date	2020-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12061361
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The Latest in Surgical Management of Stage IIIA Non-Small Cell Lung Cancer: Video-Assisted Thoracic Surgery and Tumor Molecular Profiling.

Woodard, Gavitt A / Jablons, David M

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2016 , Page(s) e435–41

Abstract: Stage IIIA non-small cell lung cancer (NSCLC) remains a treatment challenge and requires a multidisciplinary care team to optimize survival outcomes. Thoracic surgeons play an important role in selecting operative candidates and assisting with pathologic ...

Abstract	Stage IIIA non-small cell lung cancer (NSCLC) remains a treatment challenge and requires a multidisciplinary care team to optimize survival outcomes. Thoracic surgeons play an important role in selecting operative candidates and assisting with pathologic mediastinal staging via cervical mediastinoscopy, endobronchial ultrasound, or esophageal ultrasound with fine needle aspiration. The majority of patients with stage IIIA disease will receive induction therapy followed by repeat staging before undergoing lobectomy or pneumonectomy; occasionally, a patient with an incidentally found, single-station microscopic IIIA tumor will undergo resection as the primary initial therapy. Multiple large clinical trials, including SWOG-8805, EORTC-8941, INT-0139, and ANITA, have shown 5-year overall survival rates of up to 30% to 40% using triple-modality treatments, and the best outcomes repeatedly are seen among patients who respond to induction treatment or who have tumors amenable to lobectomy instead of pneumonectomy. The need for a pneumonectomy is not a reason to deny patients an operation, because current operative mortality and morbidity rates are acceptably low at 5% and 30%, respectively. In select patients with stage IIIA disease, video-assisted thoracic surgery and open resections have been shown to have comparable rates of local recurrence and long-term survival. New developments in genetic profiling and personalized medicine are exciting areas of research, and early data suggest that molecular profiling of stage IIIA NSCLC tumors can accurately stratify patients by risk within this stage and predict survival outcomes. Future advances in treating stage IIIA disease will involve developing better systemic therapies and customizing treatment plans on the basis of an individual tumor's genetic profile.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Humans ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Neoplasm Staging ; Thoracic Surgery, Video-Assisted/methods
Language	English
Publishing date	2016-07-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1548-8756 ; 1092-9118 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1092-9118 ; 1548-8748
DOI	10.14694/EdBook_AM.2015.35.e435
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Improved outcomes and staging in non-small-cell lung cancer guided by a molecular assay.

Gupta, Alexander R / Woodard, Gavitt A / Jablons, David M / Mann, Michael J / Kratz, Johannes R

Future oncology (London, England)

2021 Volume 17, Issue 34, Page(s) 4785–4795

Abstract: There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as 'early stage.' ...

Abstract	There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as 'early stage.' A 14-gene quantitative PCR-based expression profile has been extensively validated to better identify patients at high-risk of 5-year mortality after surgical resection than conventional staging - mortality that almost always results from previously undetectable metastases. Furthermore, prospective studies now suggest a predictive benefit in disease-free survival when the assay is used to guide adjuvant chemotherapy decisions in early-stage non-small-cell lung cancer patients.
MeSH term(s)	Biomarkers, Tumor/genetics ; Carcinogenesis/genetics ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/therapy ; Chemotherapy, Adjuvant/statistics & numerical data ; Clinical Decision-Making ; Datasets as Topic ; Disease-Free Survival ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Lung Neoplasms/therapy ; Molecular Diagnostic Techniques/methods ; Molecular Diagnostic Techniques/statistics & numerical data ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/prevention & control ; Neoplasm Staging/methods ; Pneumonectomy/statistics & numerical data ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Risk Assessment/methods
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2021-08-26
Publishing country	England
Document type	Journal Article ; Validation Study
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2021-0517
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6478: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Old Sonic Hedgehog, new tricks: a new paradigm in thoracic malignancies.

Giroux Leprieur, Etienne / Jablons, David M / He, Biao

Oncotarget

2018 Volume 9, Issue 18, Page(s) 14680–14691

Abstract: The Sonic Hedgehog (Shh) pathway is physiologically involved during embryogenesis, but is also activated in several diseases, including solid cancers. Previous studies have demonstrated that the Shh pathway is involved in oncogenesis, tumor progression ... ...

Abstract	The Sonic Hedgehog (Shh) pathway is physiologically involved during embryogenesis, but is also activated in several diseases, including solid cancers. Previous studies have demonstrated that the Shh pathway is involved in oncogenesis, tumor progression and chemoresistance in lung cancer and mesothelioma. The Shh pathway is also closely associated with epithelial-mesenchymal transition and cancer stem cells. Recent findings have revealed that a small proportion of lung cancer cells expressed an abnormal full-length Shh protein, associated with cancer stem cell features. In this paper, we review the role of the Shh pathway in thoracic cancers (small cell lung cancer, non-small cell lung cancer, and mesothelioma) and discuss the new perspectives of cancer research highlighted by the recent data of the literature.
Language	English
Publishing date	2018--06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.24411
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito