Cancers, Vol. 10, Pages 169: The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

Cancers, Vol. 10, Pages 169: The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

Cancers doi: 10.3390/cancers10060169

Authors: Radhia M'kacher Corina Cuceu Mustafa Al Jawhari Luc Morat Monika Frenzel Grace Shim Aude Lenain William M. Hempel Steffen Junker Theodore Girinsky Bruno Colicchio Alain Dieterlen Leonhard Heidingsfelder Claire Borie Noufissa Oudrhiri Annelise Bennaceur-Griscelli Olivier Moralès Sarah Renaud Zoé Van de Wyngaert Eric Jeandidier Nadira Delhem Patrice Carde

Background: We analyzed telomere maintenance mechanisms (TMMs) in lymph node samples from HL patients treated with standard therapy. The TMMs correlated with clinical outcomes of patients. Materials and Methods: Lymph node biopsies obtained from 38 HL patients and 24 patients with lymphadenitis were included in this study. Seven HL cell lines were used as in vitro models. Telomerase activity (TA) was assessed by TRAP assay and verified through hTERT immunofluorescence expression; alternative telomere lengthening (ALT) was also assessed, along with EBV status. Results: Both TA and ALT mechanisms were present in HL lymph nodes. Our findings were reproduced in HL cell lines. The highest levels of TA were expressed in CD30−/CD15− cells. Small cells were identified with ALT and TA. Hodgkin and Reed Sternberg cells contained high levels of PML bodies, but had very low hTERT expression. There was a significant correlation between overall survival (p < 10−3), event-free survival (p < 10−4), and freedom from progression (p < 10−3) and the presence of an ALT profile in lymph nodes of EBV+ patients. Conclusion: The presence of both types of TMMs in HL lymph nodes and in HL cell lines has not previously been reported. TMMs correlate with the treatment outcome of EBV+ HL patients.

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Immunosuppression with Antitumour Necrosis Factor Therapy Leading to Strongyloides Hyperinfection Syndrome

Strongyloides stercoralis is an endemic parasitic infection that can remain asymptomatic for years, but it can cause death in immunosuppressed individuals. Here, we present a case of Strongyloides hyperinfection in a 75-year-old male secondary to sepsis and chronic immunosuppression due to TNF-α inhibitors. Despite aggressive treatment including broad-spectrum antibiotics and antihelminths, his respiratory failure worsened and he died after palliative extubation. S. stercoralis infection remains a diagnostic challenge. Presentation with Strongyloides is often nonspecific, and eosinophilia is absent in hyperinfection. Diagnosis can be delayed, especially in low-prevalence areas where suspicion is low. Strongyloides should be considered in the differential diagnosis in the presence of risk factors including immunosuppressive therapy, and a travel history should be carefully obtained. Patients with recurrent enterobacterial sepsis or respiratory failure with diffuse infiltrates in the setting of eosinophilia should undergo testing for Strongyloides. A multidisciplinary approach can result in earlier diagnosis and favorable outcomes.

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Use of Quantitative Morphological and Functional Features for Assessment of Axillary Lymph Node in Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Background. Axillary lymph-node assessment is considered one of the most important prognostic factors concerning breast cancer survival. Objective. We investigated the discriminative power of morphological and functional features in assessing the axillary lymph node. Methods. We retrospectively analysed data from 52 consecutive patients who undergone DCE-MRI and were diagnosed with primary breast carcinoma: 94 lymph nodes were identified. Per each lymph node, we extracted morphological features: circularity, compactness, convexity, curvature, elongation, diameter, eccentricity, irregularity, radial length, entropy, rectangularity, roughness, smoothness, sphericity, spiculation, surface, and volume. Moreover, we extracted functional features: time to peak (TTP), maximum signal difference (MSD), wash-in intercept (WII), wash-out intercept (WOI), wash-in slope (WIS), wash-out slope (WOS), area under gadolinium curve (AUGC), area under wash-in (AUWI), and area under wash-out (AUWO). Selection of important features in predicting metastasis has been done by means of receiver operating characteristic (ROC) analysis. Performance of linear discriminant analysis was analysed. Results. All morphological features but circularity showed a significant difference between median values of metastatic lymph nodes group and nonmetastatic lymph nodes group. All dynamic parameters except for MSD and WOS showed a statistically significant difference between median values of metastatic lymph nodes group and nonmetastatic lymph nodes group. Best results for discrimination of metastatic and nonmetastatic lymph nodes were obtained by AUGC (accuracy 75.8%), WIS (accuracy 71.0%), WOS (accuracy 71.0%), and AUCWO (accuracy 72.6%) for dynamic features and by compactness (accuracy 82.3%), curvature (accuracy 71.0%), radial length (accuracy 71.0%), roughness (accuracy 74.2%), smoothness (accuracy 77.2%), and speculation (accuracy 72.6%) for morphological features. Linear combination of all morphological and/or of all dynamic features did not increase accuracy in metastatic lymph nodes discrimination. Conclusions. Compactness as morphological feature and area under time-intensity curve as dynamic feature were the best parameters in identifying metastatic lymph nodes on breast MRI.

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Altered DNA Methylation of Long Noncoding RNA uc.167 Inhibits Cell Differentiation in Heart Development

In previous studies, we have demonstrated the function of uc.167 in the heart development. DNA methylation plays a crucial role in regulating the expression of developmental genes during embryonic development. In this study, the methylomic landscape was investigated in order to identify the DNA methylation alterations. Methylated DNA immunoprecipitation (MeDIP) was performed to examine the differences in methylation status of overexpressed uc.167 in P19 cells. GO and KEGG pathway analyses of differentially methylated genes were also conducted. We found that the distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in intergenic regions and intron. The biological process associated with uc.167 was focal adhesion and Rap1 signaling pathway. MEF2C was significantly decreased in uc.167 overexpressed group, suggesting that uc.167 may influence the P19 differentiation through MEF2C reduction. Taken together, our findings revealed that the effect of uc.167 on P19 differentiation may be attributed to the altered methylation of specific genes.

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Involved-field chemoradiotherapy for postoperative solitary lymph node recurrence of esophageal cancer

Abstract

Background

For patients with postoperative lymph node (LN) recurrent esophageal cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains controversial. We assessed the clinical outcomes and prognostic factors related to involved-field CRT for postoperative solitary LN recurrence of esophageal squamous cell carcinoma (ESCC).

Methods

We retrospectively evaluated 21 patients who had received curative resection, with LN recurrence of ESCC. Patients received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60 Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals, and prognostic factors. We defined elective nodal failure (ENF) as recurrence in a regional LN without involved-field failure.

Results

The median follow-up duration was 32 months (range, 4–106 months). Nine patients experienced failure—4 (19%) within involved-field and 5 (24%) with distant metastasis. No patients had ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was 78%. In the univariate analysis of OS, two factors, the maximal diameter of the metastatic LN < 25 mm and the absence of serum p53 antibodies (s-p53-Abs), were associated with a significantly better prognosis (p = 0.025 and p = 0.01, respectively).

Conclusions

Involved-field CRT for postoperative solitary LN recurrence of ESCC did not cause ENF and was without severe toxicities. Two factors, a length of the metastatic LN < 25 mm and the absence of s-p53-Abs may improve the treatment outcome. Involved-field CRT is a treatment option worthy of consideration for postoperative solitary LN recurrence of ESCC.

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Mortality in Puerto Rico after Hurricane Maria

New England Journal of Medicine, Ahead of Print.


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Expression of Concern on “Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1”

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