AFP-L3 as complementary serum-marker in the diagnosis and prognosis of primary hepatocellular carcinoma (HCC)

Das Hepatozelluläre Karzinom (HCC) ist eine biologisch sehr heterogene maligne Erkrankung. Aufgrund der hohen Mortalität und weiter steigenden Inzidenz stellt diese Entität ein ernst zu nehmendes Problem dar. Kurative Ansätze sind nur in frühen Stadien möglich, jedoch wird Leberkrebs nach wie vor zu spät erkannt. Ein umfangreiches Screening ist in europäischen Ländern noch nicht etabliert. Da auch in späteren Stadien die Wahl der therapeutischen Mittel wesentlich vom Stadium der Erkrankung abhängig ist, kommt der Diagnostik insgesamt ein besonderer Stellenwert zu. In dieser Arbeit konnte in einem europäischen Patientenkollektiv bestätigt werden, dass die Sensitivität von Alfa-Fetoprotein (AFP) und Des-Gamma-Carboxyprothrombin (DCP) zur Diagnose des HCCs jeweils nicht ausreicht. Es konnte ebenfalls bestätigt werden, dass die Kombination der beiden Marker der Einzelbestimmung überlegen ist. Es wurde gezeigt, dass die Kombination aus AFP und AFP-L3 im Vergleich zu AFP und DCP vergleichbar effektiv ist. Darüber hinaus wurde belegt, dass die Kombination aller drei Tumormarker die Effektivität der Methode noch einmal deutlich steigern kann. AFP-L3 erwies sich diesbezüglich als sinnvolle Ergänzung durch teils bedeutende Sensitivitäts-Gewinne und konstant hohe Spezifität und Genauigkeit in allen untersuchten Konstellationen, einschließlich der als herausfordernd geltenden Subgruppen (Frühstadien, Zirrhotiker, eingeschränkte Leberfunktion). Es wurde deutlich, dass mit Schwellenwerten von 20 ng/ml und 10 ng/ml für AFP innerhalb der Kombination im klinischen Alltag wünschenswerte Ergebnisse erzielt werden können. Schlussendlich unterstreichen die Ergebnisse dieser Arbeit, übereinstimmend mit den neusten S3-Leitlinien, den hohen Wert der hier untersuchten Tumormarker als komplementäre, nicht invasive Untersuchungsmethode in der Diagnostik des HCCs für europäische Patienten.Primary hepatocellular carcinoma (HCC) is a biologically very heterogeneous malignant disease. Due to the high mortality and further growing incidence, this entity poses a serious risk. Curative approaches are possible only in early stages; however, liver cancer is still being identified too late. A comprehensive screening is not yet established in European countries. Since in later stages, the choosing of the therapeutic approach is also depending on the stage of the disease, diagnostics take on an essential role overall. In this paper it could be confirmed, that the sensitivity of Alfa-Fetoprotein (AFP) or Des-Gamma- Carboxyprothrombin (DCP) is not sufficient for the diagnosis of HCC. It could as well be confirmed the combination of both markers is superior to single testing. It was shown that the combination of AFP and AFP-L3 is similar effective in comparison to AFP and DCP. Further to that it could be proven, that the combination of all three tumor markers is able to increase the efficacy of this method again considerably. With regard to that, AFP-L3 proved to be a meaningful addition through partly substantial increases in sensitivity at constantly high specifity and accuracy in all examined constellations, including such subgroups considered challenging (early stages, cirrhotics, impaired liver function). It became clear that within this combination, at cut-offs of 20 ng/ml or 10 ng/ml for AFP, preferable results can be achieved in daily clinical practice. Finally, the results of this work underline, accordantly with the latest S3-Guidelines, the high value of the evaluated tumor markers as complementary, non-invasive method of investigation for the diagnosis of HCC in European patients

Melatonin Membrane Receptors in Peripheral Tissues: Distribution and Functions

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes

Antihyperglycemic activity of Tectona grandis Linn. bark extract on alloxan induced diabetes in rats

Tectona Grandis Linn.(saag - tick wood), an indigenous medicinal plant, has a folk reputation among the Indian herbs as a hypoglycemic agent. The present study was carried out to evaluate the anti-hyperglycemic effect of T. grandis Linn. bark extract in control and alloxan-diabetic rats. Oral administration of the bark suspension of T. grandis (2.5 and 5 g/kg body wt.) for 30 days resulted in a significant reduction in blood glucose (from 250 ± 6.5 to 50 ± 2.5 mg/dL). Thus, the present study clearly shows that the T. grandis Linn. bark extract exerts anti-hyperglycemic activity

Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in elderly versus non-elderly cancer patients: Patterns, outcomes, and determinants (MONITOR-GCSF study)

Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio®) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients.; Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level.; There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes.; Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG≥2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with lower rates of adverse CIN/FN events in elderly and non-elderly patients, and should be further evaluated in prospective randomized trials