��tat de sant�� et qualit�� de vie �� long terme apr��s gu��rison d��un cancer trait�� durant l��enfance

Survival of children treated for cancer has now reached 75%. Relapses are rare after five years of remission. Long term follow-up should also detect treatment related, late adverse effects. Repeated cardiac evaluations are necessary, due to cumulative dose-dependent cardiotoxicity of anthracycline. Endocrinological disorders are mainly related to radiotherapy or high dose chemotherapy. Bone mineral density can be altered. Cognitive function, academic level and social outcome of non-irradiated patients are usually normal. Incidence of second neoplasms is low, but some of them are related to previous treatments. One of the major ongoing treatment objective is to preserve the quality of life of cured patients. Improvement of patient’s information regarding late effects is also required.     

Qu��est-ce que la fragilit�� en oncog��riatrie ?

There is an increasing incidence of cancer among the aging population. This increasingly older population is heterogeneous. Optimal management of older cancer patients is challenging as the estimation of the underlying frailty guides decision-making during diagnosis until treatment commences. Frailty is a syndrome resulting from cumulative declines across multiple physiologic systems and represents a state of reduced homeostasis and resistance to stress, leading to increased vulnerability and risk of adverse outcomes such as falls, disability, hospitalization, and death. There has been increasing literature concerning frailty but a definition of the best model of frailty is still under debate. Many models have been developed and several frailty markers are now clearly identified. Few studies have used frailty markers to predict adverse outcomes due to cancer treatment and to estimate their prevalence in older cancer patients. Recommending the use of frailty markers to detect vulnerability in older cancer patients seems currently too premature. Further studies are warranted to define their use in geriatric oncology.     

M��MoPratic�� VDHA: guide de prescription pour les voies digestives hautes alt��r��es

Oral administration is often difficult for tablets or capsules when patients have nausea, vomiting, dysphagia, deglutition disorder??Howewer, specifics dosages forms are avaible. This multidisciplinary approach has allowed to build a free practical guide for optimizing medical management for upper affected gastrointestinal system. We screened Vidal Hoptimal 2010 database to collect drugs with dosages forms adapted and build a booklet and an iPhone app for best supportive care in ambulatory care. Drugs are classified by pharmaceutical, dosage form, INN, trade mark.     

MutS�� exceeds MutS�� in dinucleotide loop repair

Backround:

The target substrates of DNA mismatch recognising factors MutSα (MSH2+MSH6) and MutSβ (MSH2+MSH3) have already been widely researched. However, the extent of their functional redundancy and clinical substance remains unclear. Mismatch repair (MMR)-deficient tumours are strongly associated with microsatellite instability (MSI) and the degree and type of MSI seem to be dependent on the MMR gene affected, and is linked to its substrate specificities. Deficiency in MSH2 and MSH6 is associated with both mononucleotide and dinucleotide repeat instability. Although no pathogenic MSH3 mutations have been reported, its deficiency is also suggested to cause low dinucleotide repeat instability.

Methods:

To assess the substrate specificities and functionality of MutSα and MutSβ we performed an in vitro MMR assay using three substrate constructs, GT mismatch, 1 and 2 nucleotide insertion/deletion loops (IDLs) in three different cell lines.

Results:

Our results show that though MutSα alone seems to be responsible for GT and IDL1 repair, MutSα and MutSβ indeed have functional redundancy in IDL2 repair and in contrast with earlier studies, MutSβ seems to exceed MutSα.

Conclusion:

The finding is clinically relevant because the strong role of MutSβ in IDL2 repair indicates MSH3 deficiency in tumours with low dinucleotide and no mononucleotide repeat instability.     

Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-��B pathway

Purpose

Dihydroartemisinin (DHA) has recently shown antitumor activity in human pancreatic cancer cells. However, its effect on antiangiogenic activity in pancreatic cancer is unknown, and the mechanism is unclear. This study was aimed to investigate whether DHA would inhibit angiogenesis in human pancreatic cancer.

Methods

Cell viability and proliferation, tube formation of human umbilical vein endothelial cells (HUVECs), nuclear factor (NF)-??B DNA-binding activity, expressions of vascular endothelial growth factor (VEGF), interleukin (IL)-8, cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9 were examined in vitro. The effect of DHA on antiangiogenic activity in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice.

Results

DHA inhibited cell proliferation and tube formation of HUVECs in a time- and dose-dependent manner and also reduced cell viability in pancreatic cancer cells. DHA significantly inhibited NF-??B DNA-binding activity, so as to tremendously decrease the expression of NF-??B-targeted proangiogenic gene products: VEGF, IL-8, COX-2, and MMP-9 in vitro. In vivo studies, DHA remarkably reduced tumor volume, decreased microvessel density, and down-regulated the expression of NF-??B-related proangiogenic gene products.

Conclusions

Inhibition of NF-??B activation is one of the mechanisms that DHA inhibits angiogenesis in human pancreatic cancer. We also suggest that DHA could be developed as a novel agent against pancreatic cancer.     

Mod��lisation du risque d����volution m��tastatique chez les patients suppos��s avoir une maladie localis��e

Classification of cancer as localized or metastatic disease remains the mainstay for determining the best therapeutic strategy to be undertaken at bedside. Although simple, this classification may underestimate the risk of undetectable, early metastatic stages. Many studies have been performed to identify prognostic biomarkers for evaluating the risk of metastatic relapse in patients with apparently localized disease. Here, we have developed an original mathematical model designed to calculate a Metastatic Index. This Metastatic Index should enable to better predict the risk of invasive cancer, even when it does not show with standard imaging techniques. Further validation steps are ongoing, both in tumor-bearing animals and as part of retrospective comparisons with clinical data. This new tool should help the clinician to undertake systemic treatment at the earliest stages of the disease, thus allowing a better efficacy eventually.     

Gastric diffuse large B-cell lymphoma after the diagnosis of primary MALT lymphoma of the breast��One case report

Primary breast and gastric lymphomas as manifestations of primary extranodal lymphomas are rare malignancies, and their diagnosis, prognosis, and treatment modalities remain unclear. We report for the first time the simultaneous co-occurrence of these diseases in one patient. A 60-year-old woman was diagnosed with gastric diffuse large B-cell lymphoma (DLBCL) 2.5 years after she was found to have primary mucosa-associated lymphoid tissue (MALT) lymphoma of the breast. Although the patient underwent chemotherapy, she died of leukemia that caused irreversible cytopenia of three lineages. The data show that her MALT lymphoma apparently transfigured into gastric DLBCL. This case highlights the importance of evaluating patients for Helicobacter pylori infection when they present with extranodal MALT lymphomas, except gastric ones. Positive test findings should prompt anti-H. pylori therapy to prevent MALT lymphomas from transforming into DLBCLs.