A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors.     

Boleodorus similis n. sp. (Nematoda: Nothotylenchinae) from India

Summary A new species, B. similis, is described from male and female specimens collected from soil around roots of Plumeria acutifolia Poir from North India. It is distinguished by a short and robust body, a broad lateral field, a more posteriorly located vulva in female and the position of phasmid and the posterior extension of lateral field in male.With 8 Figures in the Text     

Anatomical variations in human carotid bodies.

The variations in anatomical structure and position of both carotid bodies were noted in 100 consecutive subjects who came to necropsy. Considerable variations in form were found. Although most carotid bodies (83% on the right and 86% on the left) were of the classic ovoid type, an appreciable minority was bilobed (9% on the right and 7% on the left) or double (7% on the right and 6% on the left); 1% were leaf shaped. All these anatomical variants have to be distinguished from the pathologically enlarged carotid body that may have a smooth or finely nodular surface. Anatomical variants (such as the bilobed) may themselves enlarge as a consequence of carotid body hyperplasia.     

Comparison of hepatitis C viral loads in patients with or without coinfection with different genotypes

Hepatitis C virus genotyping was assessed for 257 chronic hepatitis C patients with viral loads above 1,000 IU/ml. Twelve patients were coinfected with more than one genotype. Their median viral loads did not differ significantly from those observed for monoinfected patients, which in turn did not vary significantly among different genotypes.     

G-Trisomie bei akuter Erythroleukämie

Zusammenfassung Es wird über einen Fall akuter Erythroleukämie mit G-Trisomie berichtet und die mögliche Bedeutung hereditärer Faktoren für die Manifestation akuter Leukämien diskutiert.

---

Summary The cytogenetic analyses of direct bone marrow preparations in a 53 years old male with acute erythroleukaemia of 9 months disease history, revealed persistently a G-trisomy in a dominant cell line with 47 chromosomes. The peripheral blood culture preparations with phytohaemagglutinin exhibited normal diploid cell line.The frequent occurrence of akute leukaemia in Down's syndrome tempts to implicate that leukaemia with G-Trisomy having no signs of Down's syndrome is a somatic mutation initiated by some unknown hereditary recessive genes mechanisms.

     

nm23-H1 suppresses invasion of oral squamous cell carcinoma-derived cell lines without modifying matrix metalloproteinase-2 and matrix metalloproteinase-9 expression

nm23-H1 is a candidate gene for the suppression of cancer metastasis. Several studies on human breast, hepatocellular, gastric, ovarian, and colon carcinomas and melanomas have shown that reduced nm23-H1 expression was closely related to metastatic progression with poor prognosis. However, the biochemical mechanism by which nm23-H1 suppresses the metastasis has yet to be elucidated. In this study, we analyzed the correlation between nm23 expression, cell motility, and the invasive abilities of six different oral squamous cell carcinoma cell lines (HSC2, HSC3, HSC4, KB, OSC19, and OSC20). Reduced mRNA/protein expression of the nm23-H1 was observed in three cell lines (HSC2, HSC3, and HSC4). These cell lines exhibited increased cell motility and an invasive character on organotypic raft culture. On the other hand, the cell lines (KB, OSC19, and OSC20) that showed a higher expression of nm23-H1 exhibited a threefold to fivefold reduced motility and also reflected fewer invasions compared to the former three cell lines. Because the HSC3 cells demonstrated the lowest nm23-H1 expression with the highest cell motility and invasive character, we established nm23-H1-transfected HSC3 cell lines to investigate whether exogenous nm23-H1 protein could inhibit cell migration and invasive activity. These transfectants showed a significant reduction in cell motility with exogenous nm23-H1 in a dose-dependent manner, and exhibited a noninvasive character. An immunofluorescence study demonstrated a distinct stress-fiber distribution at peripheral region of these transfectants. However, no significant difference of matrix metalloproteinase (MMP)-2 and MMP-9 expression was observed between mock transfectant and nm23-H1-transfected cells. These findings suggest that nm23-H1 inhibits the invasive activity of oral squamous cell carcinoma by suppression of cell motility without altering the MMP-2 and MMP-9 status.     

Emblica officinalis Gaertn and serum cholesterol level in experimental rabbits.

Twelve albino rabbits of either sex weighing 1.0-1.25 kg were fed a standard laboratory diet of green grass and sattu (roasted Bengal gram). After a 2-week run-in period their serum cholesterol levels were estimated. All animals were now fed 0.5 g cholesterol and 1.0 g clarified butter daily and were not divided into 3 groups of 4 animals each. While all received the standard cholesterol-rich diet, Group A animals received no additional substances, animals in Group B were each fed 10 mg vitamin C daily, while those in Group C were each given 1.0 g fresh Amla (Emblica officinalis Gaertn). Mean serum cholesterol levels in all three groups rose to significantly higher levels by the end of the second week. There was a further rise by the end of the third and fourth weeks in Groups A and B. However, animals in Group C (i.e. those given Amla) showed significantly lower mean serum cholesterol levels at the end of the second week than their counterparts in Groups A and B. At the end of the third and fourth weeks the differences were even more pronounced.     

Serious complications of vascular catheter-relatedStaphylococcus aureus bacteremia in cancer patients

Over the period 1986 to 1989, 53 cancer patients were identified with catheter-relatedStaphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23 %) patients and was suspected in another 3 (6 %). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p<0.01). Fever persisted for more than three days after antibiotic initiation in 52 % of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19 % of those without complications (p<0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p<0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-relatedStaphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks.     

Molecular characterization of a complex translocation in a newborn infant

A newborn infant was referred because of low-set ears, mild downward slant of the palpebral fissues, micrognathia with higharched palate, a flat midface, small mouth, and thin upper lip with cupid bow configuration. To some extent her cry resembled that associated with cri du chat syndrome. Cytogenetic findings with G- and Q-banding alone failed to characterize precisely the complex translocations. By the chromosome in situ suppression (CISS) hybridization technique using whole chromosome specific probes, a complex 4 breakpoint rearrangement involving both arms of a single chromosome 1 with the long arms of chromosome 5 and 11 was disclosed, i.e., 46,XX, der(1),t(1;5) t(1;11) (5qter→5q31::1p31.3→1q44::11q23→11qter;5pter→5q31::1p31.3→1pter;11pter→11q23::1q44→1qter). Gene deregulation and position effect may explain the multiple anomalies in individuals with apparently balanced translocations may shed some light towards unveiling the clinical consequences associated with aberrations which are presumably balanced. © 1993 Wiley-Liss, Inc.     

Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae

Studies have indicated that purified soluble polysaccharide antigens can elicit T cell-independent Ig responses in vivo, although these responses can be modulated by T cells in a noncognate manner. Relatively little is known, however, concerning the parameters that regulate polysaccharide-specific, as well as protein-specific, Ig isotype responses to an intact extracellular bacterium. Using the murine in vivo humoral response to intact Streptococcus pneumoniae as a model it can be shown that CD4+ T-cell receptor alphabeta+ T cells deliver help for both polysaccharide- and protein-specific Ig responses. However, these responses differ fundamentally in their mechanism of action.