Multiple sclerosis in a radiosensitive family with low levels of the ATM protein

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system (CNS) characterized by demyelination associated with progressive disability. The mechanisms underlying the pathogenesis of MS remain a mystery. The highly pleiotropic syndrome known as ataxia telangiectasia (A‐T) overlaps with MS in that it also presents with demyelination in the CNS. Whether demyelination in MS or in A‐T is initiated through neuronal degeneration or immune dysfunction is not yet known. However, unlike MS, the underlying cause of A‐T is known to result from mutations in the A–T gene (ATM) that often result in the complete loss of ATM protein and loss/gain of function. ATM is implicated in neurological degeneration, particularly in the cerebellum, cellular apoptosis, immunodeficiency, double stranded deoxyribonucleic acid (DNA) rejoining, VDJ antibody recombination, tumour suppression, particularly T‐lymphoid malignancies, signal transduction, cell‐cycle control and cellular radiohypersensitivity. In this study, we describe a case of MS in a family with cellular radiosensitivity and abnormally low postinduction levels of the ATM protein. Defective DNA repair/rejoining may impact on autoimmunity.     

Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1alpha) expression in serous ovarian cancer: an immunohistochemical study

Background  

The hypoxia-inducible factor (HIF) has emerged as an attractive target for cancer therapy. The few publications addressing the prognostic significance of Hypoxia-Inducible Factor 1α (HIF-1α) cellular expression in ovarian cancer produced contradictory findings which are not permissible to widely acceptable conclusions and clinical applications. Our study was designed to investigate this by including a comparatively large number of cases and by using a combination of antibodies to analyze immunohistochemically the expression of HIF-1α.     

Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients

Based on the assumption that proteins can emanate from tumour to serum, we investigated whether serum low molecular weight proteins (LMW) can discriminate lung cancer patients from healthy donors. Pooled sera from 20 lung cancer patients matched in sex (men), histological type (adenocarcinoma) and stage (IIIB and IV) and from 20 healthy donors (men) were submitted to 2-DE coupled to MALDI-TOF peptide mass fingerprinting. Results of 2D-E/ MALDI-TOF showed five up regulated proteins (immunoglobulin lambda chain, transthyretin monomer, haptoglobin-alfa 2 and two isoforms of serum amyloid protein) and one down regulated (fragment of apolipoprotein A-I) in patients. All differentially expressed proteins, except immunoglobulin, may be acting as a non-specific sign of inflammation in cancer and transthyretin monomer may act as a possible blood marker to CSF barrier disruption that occurs, e.g., in cerebral metastasis. In conclusion, this work shows the usefulness of 2D-gel electrophoresis and mass spectrometry proteomic techniques for the identification of up- and down-regulated proteins in serum from adenocarcinoma lung cancer patients.     

Unusual complication after radiotherapy for breast cancer bronchiolitis obliterans organizing pneumonia case report and review of the literature

Breast-conserving surgery and postoperative radiotherapy play an important role in the treatment of early breast cancer. Bronchiolitis obliterans with organizing pneumonia (BOOP) is an uncommon syndrome reported to be one of the complications of adjuvant radiotherapy. We report the case of a 71-year-old woman who developed cough, dyspnea and fever three weeks after radiation therapy to the left breast for breast carcinoma. Chest X-ray and computed tomography scan demonstrated alveolar opacities within both lungs. Antibiotic therapy against any probable septic pathology did not improve the symptoms, while corticosteroid treatment resulted in rapid clinical improvement together with regression of the pulmonary opacities. Irradiation was thought to be the cause of the migratory pneumonitis, hence this case was clinically diagnosed as radiation-induced migratory pneumonitis similar to BOOP, without lung biopsy. The present case suggests that one should be mindful of this disease when treating patients with a history of irradiation to the breast. BOOP promptly responds to systemic corticosteroid therapy with rapid improvement of symptoms and regression of the pulmonary opacities.     

Benefits of six degrees of freedom for optically driven patient set-up correction in SBRT

To quantify the advantages of a 6 degrees of freedom (dof) versus the conventional 3- or 4-dof correction modality for stereotactic body radiation therapy (SBRT) treatments. Eighty-five patients were fitted with 5-7 infra-red passive markers for optical localization. Data, acquired during the treatment, were analyzed retrospectively to simulate and evaluate the best approach for correcting patient misalignments. After the implementation of each correction, the new position of the target (tumor's center of mass) was estimated by means of a dedicated stereotactic algorithm. The Euclidean distance between the corrected and the planned location of target point was calculated and compared to the initial mismatching. Initial and after correction median+/-quartile displacements affecting external control points were 3.74+/-2.55 mm (initial), 2.45+/-0.91 mm (3-dof), 2.37+/-0.95 mm (4-dof), and 2.03+/-1.47 mm (6-dof). The benefit of a six-parameter adjustment was particularly evident when evaluating the results relative to the target position before and after the re-alignment. In this context, the Euclidean distance between the planned and the current target point turned to 0.82+/-1.12 mm (median+/-quartile values) after the roto-translation versus the initial displacement of 2.98+/-2.32 mm. No statistical improvements were found after 3- and 4-dof correction (2.73+/-1.22 mm and 2.60+/-1.31 mm, respectively). Angular errors were 0.09+/-0.93 degrees (mean+/-std). Pitch rotation in abdomen site showed the most relevant deviation, being -0.46+/-1.27 degrees with a peak value of 5.46 degrees . Translational misalignments were -0.68+/-2.60 mm (mean+/-std) with the maximum value of 12 mm along the cranio-caudal direction. We conclude that positioning system platforms featuring 6-dof are preferred for high precision radiation therapy. Data are in line with previous results relative to other sites and represent a relevant record in the framework of SBRT.     

Bromodeoxyuridine Inhibits Cancer Cell Proliferation In Vitro and In Vivo

The thymidine analog bromodeoxyuridine (BrdU) is incorporated into newly synthesized DNA and has been shown to increase the susceptibility of incorporating cells to ionizing radiation. However, in the absence of secondary stressors, BrdU is thought to substitute relatively benignly for thymidine and is commonly used to “birth-date” proliferative cells. We report a novel antiproliferative effect of BrdU on cancer cells, which is independent of its role in radiosensitization. A single, brief in vitro exposure to BrdU induces a profound and sustained reduction in the proliferation rate of all cancer cells examined. Cells do not die but variably up-regulate some senescence-associated proteins as they accumulate in the G₁ phase of the cell cycle. Bromodeoxyuridine also impairs the proliferative capacity of primary tumor-initiating human glioma cells and may therefore represent a means of targeting cancer stem cells. Finally, conservative in vivo BrdU regimens—in the absence of any other treatment—significantly suppress the progression of gliomas in the highly aggressive, syngeneic RG2 model. These results suggest that BrdU may have an important role as an adjunctive therapeutic for a wide variety of cancers based on new insights into its effect as a negative regulator of cell cycle progression.     

Clinicopathological features of primary cutaneous B-cell lymphomas from an academic regional hospital in central Italy: no evidence of Borrelia burgdorferi association

We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.     

Comparison of intra-aortic computed tomography angiography to conventional angiography in the presurgical visualization of the Adamkiewicz artery: first results in patients with thoracoabdominal aortic aneurysms

Introduction

The aim of this study was to compare the sensitivity of intra-aortic computed tomography angiography (IA-CTA) to that of regular spinal digital subtraction angiography for the presurgical location of the Adamkiewicz artery (AKA).

Methods

Thirty patients (21 males, 9 females; mean age 64 years) had an IA-CTA for the location of the AKA before surgery of aneurysm (n?=?24) or dissection (n?=?6) of the thoracoabdominal aorta. After femoral artery puncture, a pigtail catheter was positioned at the origin of the descending aorta. CT acquisition was performed with an intra-aortic iodinated contrast media injection (15 mL/s, 120 mL). The visualization of the AKA and the location of the feeder(s) to the AKA were independently evaluated by two observers. Interrater agreement was calculated using a kappa test. Spinal angiogram by selective catheterization was systematically performed to confirm the results of the IA-CTA.

Results

The AKA was visualized by the IA-CTA in 27/30 cases (90 %); in 26/31 (84 %) cases, the continuity with the aorta was satisfactorily seen. Interrater agreement was good for the visualization of the AKA and its feeder(s): 0.625 and 0.87, respectively. In 75 % of the cases for which the AKA was visualized, the selective catheterization confirmed the results of the IA-CTA. In the remaining 25 % of the cases, the selective catheterization could not be performed due to marked vessels’ tortuosity or ostium stenosis.

Conclusion

IA-CTA is a feasible technique in a daily practice that presents a good sensitivity for the location of the AKA.