Cytokine-induced killer cells are type II natural killer T cells

Background: Until now, cytokine-induced killer (CIK) cells were assumed to be part of the type I natural killer T (NKT) cell population, but it was not yet investigated if this is correct

High-dose chemotherapy with autologous peripheral blood stem cell support for recurrent primary AFP-producing intracranial germinoma

We report of a 34-year old man with second intracranial relapse of a suprasellar germinoma. Despite of extensive pretreatment with radiation and conventional chemotherapy relapse occurred and was treated with sequential high-dose chemotherapy followed by transfusion of autologous peripheral stem cells. The high-dose chemotherapy course was complicated by refractory derailment of pineal gland insufficiency. The patient achieved a complete remission after high dose chemotherapy which lasted for 13 months. Subsequently, he developed a third relapse and died

Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

Objective: Therapeutic vaccination with dendritic cells (DC) showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC). Human telomerase reverse transcriptase (hTERT) could be a potential target because it is detectable in more than 85% of human tumors including RCC

an interim analysis from the prospective GMMG-MM5 trial

We investigated the impact of subcutaneous versus intravenous bortezomib in the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared bortezomib, doxorubicin, and dexamethasone with bortezomib, cyclophosphamide, and dexamethasone induction therapy in newly diagnosed multiple myeloma. Based on data from relapsed myeloma, the route of administration for bortezomib was changed from intravenous to subcutaneous after 314 of 604 patients had been enrolled. We analyzed 598 patients who received at least one dose of trial medication. Adverse events were reported more frequently in patients treated with intravenous bortezomib (intravenous=65%; subcutaneous=56%, P=0.02). Rates of grade 2 or more peripheral neuropathy were higher in patients treated with intravenous bortezomib during the third cycle (intravenous=8%; subcutaneous=2%, P=0.001). Overall response rates were similar in patients treated intravenously or subcutaneously. The presence of International Staging System stage III disease, renal impairment or adverse cytogenetic abnormalities did not have a negative impact on overall response rates in either group. To our knowledge this is the largest study to present data comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma. We show better tolerance and similar overall response rates for subcutaneous compared to intravenous bortezomib. The clinical trial is registered at eudract.ema.europa.eu as n. 2010-019173-16

Primary small cell carcinoma of the esophagus: patient data metaanalysis and review of the literature [Primäres kleinzelliges Ösophaguskarzinom: Patientendaten-Metaanalyse und Review der Literatur ]

[english] We analysed the typical features of primary small cell carcinoma of the esophagus (SCCE) with emphasis on occurrence, behaviour, outcome and treatment options. This metaanalysis was aimed at collecting and analyzing information from international studies about handling this disease. This seems necessary due to the rarity of this disease. Studies were acquired from electronic databases and reference lists. We finally analysed 313 patient cases from the literature with oesophageal SCC. A data extraction was accomplished referring to 13 evaluable features that are described in the “methods”, whereof 7 were analyzed with univariate and multivariate tests. Three hundred thirteen cases were analyzed, 109 patients (35%) had limited stage (LS), whereas 167 (54%) had extensive stage (ES). There is no information about the remaining 35 patients concerning the stage. Univariate and multivariate analysis showed only age (<50 years vs. >50 years, HR 1.024; 95% CI 1.000–1.041, <0.0001) and disease stage (LS vs. ES, HR 4.884; 95% CI 2.572–9.27, <0.0001) as significant prognostic factors. There also was a statistically significant difference in survival between those patients who received therapy compared to those who only received best supportive care (11.6 months vs. 0.8 months, HR 0.093, CI 95% 0.053–0.16, <0.001). In this first multivariate analysis for SCCE we show that SCCE is an aggressive type of tumour with a shorter survival rate compared to its counterpart from the lung. It is demonstrated that only disease stage (limited vs. extensive stage), age (<50 years vs. >50 years) and therapy are independent significant predictors of prognosis.<br>[german] Gegenstand unserer Untersuchungen war die Erhebung typischer Eigenschaften des kleinzelligen Ösophaguskarzinoms mit Berücksichtigung des Auftretens, des Verlaufs, der Auswirkung und der Behandlungsoptionen. Ziel unserer Metaanalyse bestand darin, Informationen aus internationalen Studien, die sich mit dieser Krankheit befassten, zu sammeln und auszuwerten. Dies scheint notwendig aufgrund der Seltenheit der Krankheit. Die verwendeten Studien wurden von elektronischen Datenbanken und Referenzlisten ermittelt. Insgesamt wurden 313 Patientenfälle mit einem kleinzelligen Ösophaguskarzinom aus der Literatur ausgewertet. Die erhobenen Daten beziehen sich auf 13 auswertbare Kriterien, die in den „Methoden“ beschrieben sind, wovon sieben Kriterien mit univariaten und multivariaten Tests untersucht worden sind. Von 313 analysierten Patientenfällen waren 109 (35%) Patienten im limitierten Stadium der Erkrankung und 167 (54%) im ausgedehnten Stadium. Über die übrigen 35 Patienten sind keine Informationen bezüglich des Stadiums bekannt. Univariate und multivariate Analysen zeigten nur das Alter (<50 Jahre vs. >50 Jahre, HR 1.024; 95% CI 1.000–1.041, <0.0001) und das Krankheitsstadium (LS vs. ES, HR 4.884; 95% CI 2.572–9.27, <0.0001) als signifikante prognostische Faktoren. Ebenfalls gab es einen statistisch signifikanten Unterschied in der Überlebenschance zwischen jenen Patienten, die therapiert worden sind, und jenen, die außer bestmöglicher unterstützender Fürsorge nicht therapiert worden sind (11,6 Monate vs. 0,8 Monate, HR 0.093, CI 95% 0.053–0.16, <0.001). In dieser ersten multivariaten Analyse für das kleinzellige Ösophaguskarzinom zeigen wir, dass diese Form des Krebses eine sehr aggressive Form ist, die mit einer kürzeren Überlebensrate einhergeht verglichen mit seinem Pendant, dem kleinzelligen Bronchialkarzinom. Es wurde gezeigt, dass nur das Krankheitsstadium (limitiert vs. ausgedehnt), das Alter (<50 Jahre vs. >50 Jahre) und die Therapie als Kriterien eigenständige, signifikante Anzeichen für eine Prognose sind

Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells

Previously we described an involvement of the C-type lectin receptor CD94 and the neuronal adhesion molecule CD56 in the interaction of natural killer (NK) cells with Hsp70-protein and Hsp70-peptide TKD. Therefore, differences in the cell surface density of these NK cell–specific markers were investigated comparatively in CD94-sorted, primary NK cells and in established NK cell lines NK-92, NKL, and YT after TKD stimulation. Initially, all NK cell types were positive for CD94; the CD56 expression varied. After stimulation with TKD, the mean fluorescence intensity (mfi) of CD94 and CD56 was upregulated selectively in primary NK cells but not in NK cell lines. Other cell surface markers including natural cytotoxicity receptors remained unaffected in all cell types. CD3-enriched T cells neither expressing CD94 nor CD56 served as a negative control. High receptor densities of CD94/CD56 were associated with an increased cytolytic response against Hsp70 membrane–positive tumor target cells. The major histocompatibility complex (MHC) class I–negative, Hsp70-positive target cell line K562 was efficiently lysed by primary NK cells and to a lower extent by NK lines NK-92 and NKL. YT and CD3-positive T cells were unable to kill K562 cells. MHC class-I and Hsp70-positive, Cx+ tumor target cells were efficiently lysed only by CD94-sorted, TKD-stimulated NK cells with high CD94/CD56 mfi values. Hsp70-specificity was demonstrated by antibody blocking assays, comparative phenotyping of the tumor target cells, and by correlating the amount of membrane-bound Hsp70 with the sensitivity to lysis. Remarkably, a 14-mer peptide (LKD), exhibiting only 1 amino acid exchange at position 1 (T to L), neither stimulated Hsp70-reactivity nor resulted in an upregulated CD94 expression on primary NK cells. Taken together our findings indicate that an MHC class I–independent, Hsp70 reactivity could be associated with elevated cell surface densities of CD94 and CD56 after TKD stimulation