Focus: Thrombopoietin-Increased DNA-PK-Dependent DNA Repair Limits Hematopoietic Stem and Progenitor Cell Mutagenesis in Response to DNA Damage

Abstract

DNA double-strand breaks (DSBs) represent a serious threat for hematopoietic stem cells (HSCs). How cytokines and environmental signals integrate the DNA damage response and contribute to HSC-intrinsic DNA repair processes remains unknown. Thrombopoietin (TPO) and its receptor, Mpl, are critical factors supporting HSC self-renewal and expansion. Here, we uncover an unknown function for TPO-Mpl in the regulation of DNA damage response. We show that DNA repair following γ-irradiation (γ-IR) or the action of topoisomerase-II inhibitors is defective in Mpl(-/-) and in wild-type mouse or human hematopoietic stem and progenitor cells treated in the absence of TPO. TPO stimulates DNA repair in vitro and in vivo by increasing DNA-PK-dependent nonhomologous end-joining efficiency. This ensures HSC chromosomal integrity and limits their long-term injury in response to IR. This shows that niche factors can modulate the HSC DSB repair machinery and opens new avenues for administration of TPO agonists for minimizing radiotherapy-induced HSC injury and mutagenesis.

Source: Thrombopoietin-Increased DNA-PK-Dependent DNA Repair Limits Hematopoietic Stem and Progenitor Cell Mutagenesis in Response to DNA Damage. de Laval B, Pawlikowska P, Petit-Cocault L, Bilhou-Nabera C, Aubin-Houzelstein G, Souyri M, Pouzoulet F, Gaudry M, Porteu F (francoise.porteu@inserm.fr). Cell Stem Cell. 2013 Jan 3;12(1):37-48.

Free paper available at:

http://download.cell.com/cell-stem-cell/pdf/PIIS1934590912006352.pdf?intermediate=true

LIST OF TUMOR MORPHOLOGIES (PART 9) - LISTE DE MORPHOLOGIES TUMORALES (PARTIE 9)

LIST OF TUMOR MORPHOLOGIES:

Tumor types are classified according to the International Classification of Diseases for Oncology (ICD-O), 3rd Edition, World Health Organization, Geneva, 2000. The ICD-O-3 is a dual classification and coding system for both morphology and topography of a neoplasm.

The MORPHOLOGY code (Mxxxx/x) indicates the specific histologic term.

The TOPOGRAPHY code (C00-C80) is occasionally mentioned here.

Abbreviation: NOS, not otherwise specified

LISTE DE MORPHOLOGIES TUMORALES

Les types de tumeurs sont classés en fonction de la « Classification Internationale des Maladies pour l'Oncologie (CIM-O), 3e édition, Organisation mondiale de la Santé, Genève, 2000. La CIM-O-3 est un système de classification et de codage pour la morphologie et la topographie d'une tumeur.

Le code de MORPHOLOGIE (Mxxxx/x) indique le terme spécifique histologique.

Le code de TOPOGRAPHIE (C00-C80) est occasionnellement mentionné ici.

Abréviation: SAI, sans autre indication

M843 Tumeurs muco-épidermoïdes

M843	MUCOEPIDERMOID CARCINOMA	CARCINOME MUCO-ÉPIDERMOÏDE
M8430/3	Mucoepidermoid carcinoma
	Carcinome muco-épidermoïde

M844-M849 Néoplasmes kystiques, muqueux et séreux

M844	CYSTADENOCARCINOMA, NOS	CYSTADÉNOCARCINOME, SAI
M8440/3	Cystadenocarcinoma, NOS
	Cystadénocarcinome, SAI
M8441/3	Serous cystadenocarcinoma, NOS		C56.9
	Cystadénocarcinome séreux SAI
M8442/1	Serous cystadenoma, borderline malignancy		C56.9
	Cystadénome séreux à la limite de la malignité

M845	PAPILLARY CYSTADENOCARCINOMA, NOS	CYSTADÉNOCARCINOME PAPILLAIRE, SAI
M8450/3	Papillary cystadenocarcinoma, NOS		C56.9
	Cystadénocarcinome papillaire SAI
M8451/1	Papillary cystadenoma, borderline malignancy		C56.9
	Cystadénome papillaire à la limite de la malignité
M8452/3	Solid pseudopapillary carcinoma		C25._
	Carcinome pseudo-papillaire solide
M8453/2	Intraductal papillary-mucinous carcinoma, non invasive		C25._
	Carcinome intracanalaire mucineux et papillaire, non-invasif
M8453/3	Intraductal papillary-mucinous carcinoma, invasive		C25._
	Carcinome intracanalaire mucineux et papillaire, invasif

           

M846	PAPILLARY SEROUS CYSTADENOCARCINOMA	CYSTADÉNOCARCINOME SÉREUX PAPILLAIRE
M8460/3	Papillary serous cystadenocarcinoma		C56.9
	Cystadénocarcinome séreux papillaire
M8461/3	Serous surface papillary carcinoma		C56.9
	Carcinome séreux papillaire de surface
M8462/1	Serous papillary cystic tumor of borderline malignancy		C56.9
	Tumeur kystique séreuse papillaire à la limite de la malignité

M847	MUCINOUS CYSTADENOCARCINOMA, NOS	CYSTADÉNOCARCINOME MUCINEUX, SAI
M8470/2	Mucinous cystadenocarcinoma, non-invasive		C25._
	Cystadénocarcinome mucineux, non-invasif
M8470/3	Mucinous cystadenocarcinoma, NOS		C56.9
	Cystadénocarcinome mucineux, SAI
M8471/3	Papillary mucinous cystadenocarcinoma		C56.9
	Cystadénocarcinome mucineux papillaire
M8472/1	Mucinous cystic tumor of borderline malignancy		C56.9
	Tumeur kystique mucineuse à la limite de la malignité
M8473/1	Papillary mucinous cystadenoma of borderline malignancy		C56.9
	Cystadénome papillaire mucineux à la limite de la malignité

M848	MUCINOUS ADENOCARCINOMA	ADÉNOCARCINOME MUCINEUX
M8480/3	Mucinous adenocarcinoma
	Adénocarcinome mucineux
M8481/3	Mucin-producing adenocarcinoma
	Adénocarcinome mucipare
M8482/3	Mucinous adenocarcinoma, endocervical type
	Adénocarcinome mucineux endocervical

M849	SIGNET RING CELL CARCINOMA	CARCINOME À CELLULES EN BAGUE À CHATON
M8490/3	Signet ring cell carcinoma
	Carcinome à cellules en bague à chaton

Focus: Prognostic value of alpha-fetoprotein and des-gamma-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization

ABSTRACT:

Background/Aims: Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have been used as diagnostic tools for hepatocellular carcinoma (HCC). However, prediction of outcome using AFP and DCP has not been elucidated. We investigated the clinical role of AFP and DCP as predictors of treatment outcome in patients with HCC undergoing trans-arterial chemoembolization (TACE).

METHODS:

Between January 2003 and December 2005, we enrolled 115 treatment-naive patients who received TACE as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 50% from the baseline level 1 month after TACE. Patients with AFP < 20 ng/mL or DCP < 20 mAU/mL were excluded.

RESULTS:

The median age was 59 years and the male gender predominated (n = 81, 70.4%). AFP and DCP response was identified in 91 (79.1%) and 77 (66.9%) patients after TACE. Although progression-free survival (PFS) did not differ according to AFP response (P = 0.150), AFP responders showed significantly better overall survival (OS) than non-responders (34.9 vs. 13.2 months; P = 0.002). In contrast, DCP response did not influence either PFS or OS (all P > 0.05). Multivariate analyses showed that gamma-glutamyltranspeptidase and baseline AFP were predictors of PFS (all P < 0.05) and that male gender, the presence of liver cirrhosis, baseline DCP, number of measurable tumors and AFP response were independent predictors of OS (all P < 0.05).

CONCLUSIONS:

AFP response and higher baseline DCP level are significant predictors of OS in treatment-naive patients with HCC receiving TACE who showed pretreatment elevation of both AFP and DCP.

Source: Prognostic value of alpha-fetoprotein and des-gamma-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Lee YK, Kim SU, Kim DY, Ahn SH, Lee KH, Lee DY, Han KH, Chon CY, Park JY (DRPJY@yuhs.ac). BMC Cancer. 2013 Jan 3;13(1):5.

Free paper available at:

http://www.biomedcentral.com/content/pdf/1471-2407-13-5.pdf

Focus: American Society of Clinical Oncology Statement: Achieving High-Quality Cancer Survivorship Care.

Source: American Society of Clinical Oncology Statement: Achieving High-Quality Cancer Survivorship Care. McCabe MS, Bhatia S, Oeffinger KC, Reaman GH, Tyne C, Wollins DS, Hudson MM (melissa.hudson@stjude.org). J Clin Oncol. 2013 Jan 7.

Free paper available at:

http://jco.ascopubs.org/content/early/2013/01/07/JCO.2012.46.6854.full.pdf+html