Determination of neptunium in environmental samples by extraction chromatography after valence adjustment

Neptunium(V) ions are unstable in acid media, which limits their extraction on chromatographic resins. We developed a novel analytical method to measure Np by either α-spectrometry or inductively coupled plasma mass spectrometry (ICP-MS) after extraction chromatography as Np(VI). We investigated the reactivity of various oxidizing reagents, and determined the retention capacity of Np(IV, V, and VI) on various extraction chromatographic supports. A simple method using two UTEVA resins was used to rapidly detect Np in soil and sediment samples.     

Photon scatter in portal images: physical characteristics of pencil beam kernels generated using the EGS Monte Carlo code

Pencil beam kernels describing scattered photon fluence behind homogeneous water slabs at various air gap distances were generated using the EGS Monte Carlo code. Photon scatter fluence was scored in separate bins based on the particle's history: singly scattered, multiply scattered, and bremsstrahlung and positron annihilation photons. Simultaneously, the mean energy and mean angle with respect to the incident photon pencil beam were tallied. Kernels were generated for incident photon pencil beams exhibiting monoenergetic spectra of 2.0 and 10.0 MeV, and polyenergetic spectra representative of 6 and 24 MV beams. Reciprocity was used to generate scatter fractions on the central axis for various field sizes, phantom thicknesses, and air gaps. The scatter kernels were further characterized by full width at half-maximum estimates. Modulation transfer functions were calculated, providing theoretical estimates of the limit of performance of portal imaging systems due to the intrinsic scattering of photon radiation through the patient.     

Quantitation of human herpesvirus-6A, -6B and -7 DNAs in whole blood, mononuclear and polymorphonuclear cell fractions from healthy blood donors

Background

Diagnosis of human herpesvirus-6A (HHV-6A), -6B (HHV-6B) or -7 (HHV-7) infections is often based on the measure of viral load in blood.

Objectives

The aim of this study was to define usual values of HHV-6A, HHV-6B and HHV-7 loads in blood fractions (whole blood [WB], mononuclear cells [PBMCs], polymorphonuclear leukocytes [PMNLs]) of blood donors.

Study design

HHV-6A, HHV-6B and -7 DNAs were quantitated using real-time PCR assays in WB, PBMCs and PMNLs separated on Ficoll or dextran gradients, respectively, for 200 blood donors. Viral loads were expressed as the number of viral genomic copies per million cells (Cop/M) for all fractions, and also per milliliter for WB.

Results

HHV-6B DNA was rarely detected in WB (8%), PBMCs (16.5%), and PMNLs (10.5%), HHV-6A was never detected, whereas HHV-7 DNA was often present in WB (51.5%), PBMCs (62%) and PMNLs (51.5%). Median loads were low with 81 Cop/M in WB, 62 Cop/M in PBMCs and 34.5 Cop/M in PMNLs for HHV-6B, and 129 Cop/M in WB, 225 Cop/M in PBMCs and 62 Cop/M in PMNLs for HHV-7. Viral load expression per million cells and per mL were equivalent. One subject had chromosomally integrated HHV-6 with high viral loads ranging from 2.23 × 10⁶ to 3.21 × 10⁶ Cop/M in all compartments and plasma.

Conclusions

These results allow to propose viral load in WB as a sensitive and suitable marker, with values for healthy subjects at approximately 100 Cop/M for both viruses. The prevalence of chromosomally integrated HHV-6 was 0.5%.     

Metachronous multicentric giant-cell tumor of the bone in the lower limb. Case report and Ki-67 immunohistochemistry study

Multicentric giant-cell tumors of the bone (GCTs) are rare. Little is known about the mechanisms by which these tumors spread and how 1% of GCT turn out to be multicentric. We report the case of a 19-year-old woman with metachronous multiple and recurrent GCTs that were unusual in their pattern of progression along the right lower limb over a 23-year period. Histology showed no evidence of malignant transformation. The treatment was repeated curettage and packing with cement. This did not permit a wide surgical margin, but avoided amputation and preserved full limb function. We tested the proliferation index marker Ki-67 in the tumor specimens. Ki-67 expression was limited to the mononuclear cell component of the tumors. The proliferation index was similar in each new tumor and higher in recurrences for each location. In this case, proliferation was initially low in the new tumor location, despite the time difference and independent from the initial clone evolution. Proliferation index increased in recurrent GCTs after marginal margin resection.     

Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction

To examine the biological impact of locally expressed stromal cell-derived factor-1α (SDF-1α) during the acute phase of remodeling after myocardial infarction (MI), rats were treated with the selective CXCR4 receptor antagonist AMD3100 (1 mg/kg; given 24 h post-MI and continued for 6 days). In 1-week post-MI rats, intense SDF-1 immunoreactivity was detected in scar-residing vessels, and SDF-1α messenger ribonucleic acid (mRNA) levels were significantly greater in the infarct region compared to the noninfarcted left ventricle (NILV). AMD3100 treatment of post-MI rats reduced infarct size, improved systolic function, and partially suppressed the increased expression of atrial natriuretic peptide mRNA in the NILV. The latter finding indirectly suggests that SDF-1α may have contributed to the hypertrophic response of the NILV. SDF-1α treatment of neonatal rat ventricular myocytes (NNVMs) failed to promote protein synthesis. However, in hypertrophied NNVMs, SDF-1α treatment further augmented ³H-leucine uptake, and AMD3100 selectively inhibited the increase in protein synthesis. Collectively, these data support the existence of an SDF-1α gradient in the damaged rat myocardium increasing toward the infarct region and highlight the novel observation that AMD3100 antagonism of the SDF-1α/CXCR4 axis reduced scar expansion and improved contractility. In vitro data further suggest that SDF-1α may have contributed to the hypertrophic response of the NILV.     

Pr?ventive Chirurgie des vererbten colorectalen Carcinoms als Folge molekularer Diagnostik

Zahlreiche vererbte Genver?nderungen, die zu Krebs pr?disponieren, sind bekannt und ihre Zahl nimmt st?ndig zu. Die pr?zise Voraussage des individuellen Risikos im Rahmen der molekularen Diagnostik hat klinische Konsequenzen bei der Behandlung von Krebspr?dispositionssyndromen. Wir zeigen am Beispiel der famili?ren adenomat?sen Polyposis (FAP) und dem heredit?ren nichtpolyposis assoziierten colorectalen Carcinomsyndrom (HNPCC) wie die zugrundeliegenden Genver?nderungen zur Tumorentstehung beitragen und mittels molekulardiagnostischer Methoden effizient identifiziert werden k?nnen. Die Kenntnis der famili?ren Keimbahnmutation erlaubt es, innerhalb von betroffenen Familien Mutationstr?ger und Nichtmutationstr?ger voneinander zu unterscheiden. Damit ist ein individuell zugeschnittenes klinisches überwachungsprogramm m?glich. Diese Entwicklung auf der Grundlage der molekularen Diagnostik findet ihre konsequente Fortsetzung in pr?ventiven chirurgischen Therapiema?nahmen, deren Indikationen diskutiert werden sollen.     

Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy

Background

Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment.

Objective

To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC.

Patients and Methods

For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib. The expression of c-MET was correlated with pathological, immunohistochemical (VEGFA, CAIX, PD-L1), clinical, and molecular criteria (VHL status) by univariate and multivariate analyses and to clinical outcome using Kaplan-Meier curves compared by log-rank test.

Results

Of ccRCC, 31.1% had low c-MET expression (absent to weak intensity by IHC) versus 68.9% with high expression (moderate to strong intensity). High expression of c-MET was associated with a gain in FISH analysis (p=0.004), sarcomatoid component (p=0.037), and PD-L1 (p<0.001) after logistic regression. No difference was observed in clinical outcomes.

Conclusion

This study is the first to analyse c-MET status in metastatic ccRCC. The high expression of c-MET in the majority of ccRCC and its independent association with PD-L1 expression, may suggest a potential benefit from combining c-MET inhibitors and targeted immunotherapy.

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Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families

Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifetime risk in gene carriers for synchronous and for metachronous colorectal cancer and endometrial cancer in women, prophylactic and extended surgery are considered as options for gene carriers. A 54-year-old patient with a history of metachronous rectal cancer and a family history fulfilling the Amsterdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histological examination of the specimen showed three synchronous colon carcinomas. The 31-year-old son carrying the pathogenic mutation refused to be included in the HNPCC surveillance program. One year later he presented with symptoms of bowel obstruction, and a carcinoma of the descending colon was diagnosed. Intraoperatively, in addition to the colon cancer, a small bowel cancer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented with synchronous cancer of the ascending colon and the lower rectum at the age of 49 years. Proctocolectomy and prophylactic hysterectomy were performed, which revealed an additional colon cancer and endometrial cancer. We discuss approaches for individual decision making for surgery in HNPCC patients. Is a subtotal colectomy indicated in the case of first colon cancer in HNPCC patients, or if the first tumor occurs in the lower rectum, should a proctocolectomy or a restorative proctocolectomy be considered? The aim of prospective clinical studies should be to assess acceptability, survival rates, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophylactic surgery.