Παρασκευή, 28 Ιουλίου 2017

Predictive biomarkers of resistance to hypofractionated radiotherapy in high grade glioma

Abstract

Background

Radiotherapy plays a major role in the management of high grade glioma. However, the radioresistance of glioma cells limits its efficiency and drives recurrence inside the irradiated tumor volume leading to poor outcome for patients. Stereotactic hypofractionated radiotherapy is one option for recurrent high grade gliomas. Optimization of hypofractionated radiotherapy with new radiosensitizing agents requires the identification of robust druggable targets involved in radioresistance.

Methods

We generated 11 xenografted glioma models: 6 were derived from cell lines (1 WHO grade III and 5 grade IV) and 5 were patient derived xenografts (2 WHO grade III and 3 grade IV). Xenografts were treated by hypofractionated radiotherapy (6x5Gy). We searched for 89 biomarkers of radioresistance (39 total proteins, 26 phosphoproteins and 24 ratios of phosphoproteins on total proteins) using Reverse Phase Protein Array.

Results

Both type of xenografted models showed equivalent spectrum of sensitivity and profile of response to hypofractionated radiotherapy. We report that Phospho-EGFR/EGFR, Phospho-Chk1/Chk1 and VCP were associated to resistance to hypofractionated radiotherapy.

Conclusions

Several compounds targeting EGFR or CHK1 are already in clinical use and combining them with stereotactic hypofractionated radiotherapy for recurrent high grade gliomas might be of particular interest.



http://ift.tt/2v6hn9u

Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma

Abstract

Purpose

This large, population-based U.S. study of lymphoma patients followed for up to four decades enables detailed analysis of second primary mesothelioma risk after radiotherapy.

Methods

U.S. Surveillance, Epidemiology, and End Results data were used to identify second primary mesothelioma among patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) between 1973 and 2014. Standardized incidence ratios (SIRs) were calculated by radiotherapy. Multivariate adjusted associations were examined using competing risks survival analysis.

Results

Among 47,219 HL patients (19,538 irradiated) and 252,090 NHL patients (52,454 irradiated), second primary mesothelioma developed among 28 lymphoma patients who received radiotherapy and 59 who did not. Mesothelioma risk was increased among HL and NHL patients treated with radiotherapy [SIR = 1.78, 95% confidence interval (CI) 1.18–2.58], but not without radiotherapy. After multivariate adjustment, radiotherapy was associated with increased mesothelioma risk (relative risk = 1.64, 95% CI 1.05–2.57), especially in lymphoma patients diagnosed before 1995 and after a latency of at least 10 years, and apparently with younger age at diagnosis.

Conclusions

The increase in second primary mesothelioma risk following radiotherapy for lymphoma is independent of several patient and disease characteristics, and is higher with earlier treatment era and longer latency.



http://ift.tt/2tJIt2G

Extraneuraxial metastases in medulloblastoma: is histology and molecular biology important?



http://ift.tt/2h8zsyi

Nuclear localization of Metabolic enzymes in Immunity and Metastasis

Publication date: Available online 27 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Yuchen He, Menghui Gao, Yiqu Cao, Haosheng Tang, Shuang Liu, Yongguang Tao
Metabolism is essential to all living organisms that provide cells with energy, regulators, building blocks, enzyme cofactors and signaling molecules, and is in tune with nutritional conditions and the function of cells to make the appropriate developmental decisions or maintain homeostasis. As a fundamental biological process, metabolism state affects the production of multiple metabolites and the activation of various enzymes that participate in regulating gene expression, cell apoptosis, cancer progression and immunoreactions. Previous studies generally focus on the function played by the metabolic enzymes in the cytoplasm and mitochondrion. In this review, we conclude the role of them in the nucleus and their implications for cancer progression, immunity and metastasis.



http://ift.tt/2w6iLWW

de Garengeot hernia with appendicitis treated by two-way-approach surgery: a case report

m_rjx140f01.png?Expires=1501335303&Signa

Abstract
de Garengeot hernia is a rare subtype of a femoral hernia with incarceration of the appendix. This type of hernia usually presents with therapeutic dilemmas, especially because of the risk of surgical site infection (SSI). Our patient was a 74-year-old woman with a bulging mass and tenderness in the right inguinal area. Computed tomography revealed an incarcerated appendix, with appendicitis in the femoral hernia. Laparoscopic appendectomy was initially performed, followed by hernioplasty via the anterior approach to prevent properitoneal contamination. Some authors have recently reported cases successfully treated by laparoscopy. However, this type of hernia has a higher risk for SSI, compared with the risk involved in usual hernioplasty. Therefore, selection of the appropriate surgical approach to prevent wound infection is important, especially in the presence of appendicitis. We would like to highlight the usefulness of hybrid surgery, laparoscopic appendectomy and hernioplasty via the anterior approach to prevent SSIs.

http://ift.tt/2uJ5YdE

Acute presentation of congenital diaphragmatic hernia requiring damage control laparotomy in an adult patient

m_rjx144f01.png?Expires=1501335315&Signa

Abstract
Congenital diaphragmatic hernias constitute an infrequent but potentially serious presentation of bowel obstruction in the adult patient. Herein, we present a rare case of an adult patient with strangulation of colon within a Morgagni's hernia where timely recognition and intervention were life-saving. An 18-year-old female presented with an acute abdomen, respiratory failure, and shock secondary to a strangulated, previously undiagnosed Morgagni hernia requiring emergency laparotomy, reduction of hernia contents and resection of non-viable colon. The patient underwent repair of the hernia with restoration of bowel continuity and reconstruction of her abdominal wall in sequential fashion. Although congenital diaphragmatic hernias have been previously described in the adult population, there are few if any reports of such pathology presenting in such an acute, life-threatening fashion. This case highlights the importance of a high index of suspicion, early recognition, and timely surgical intervention for this rare, potentially fatal condition.

http://ift.tt/2uIT6nJ

Dislocation of a mandibular condyle in the middle cranial fossa, diagnosed 54 years after trauma

m_rjx149f01.png?Expires=1501334789&Signa

Abstract
Dislocation of the mandibular condyle into the middle cranial fossa is a rare complication of mandibular trauma. We report the remarkable case of a 63-year-old patient in whom trauma 54 years prior to consultation resulted in intrusion of the right mandibular condyle into the middle cranial fossa. The diagnosis was missed because of insufficient data provided by conventional radiographies. Failure of timely diagnosis and lack of appropriate treatment resulted in temporomandibular joint ankylosis with functional impairment, disturbance of mandibular growth and dentofacial asymmetry. We emphasize the need for careful radiological investigation in case of a suspected condylar fracture or dislocation, especially when the mechanism of injury is likely to facilitate condylar intrusion. The use of CT and MR-imaging is therefore advocated.

http://ift.tt/2uIVo6w