Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Isolation and characterization of Bacillus thuringiensis (Ernst Berliner) strains indigenous to agricultural soils of Mali.

The objective of this work was to isolate and characterize Bacillus thuringiensis from agricultural and other insect breeding sites in Mali. A hundred soil samples were collected from Bamako district, Segou, Sikasso and Timbuktu regions. B. thuringiensis (Bt) was isolated from the samples using a heat-acetate method and the isolates were identified and classified using morphological and biochemical tests. The frequency of B. thuringiensis in soils was noted. The results showed that, 15 out of the 3111 bacterial isolates were putative Bt. thuringiensis. Most isolates produced parasporal crystals. The average Bt index for all the areas sampled was 5.1%; the highest frequency was recorded for Niono in Segou region (11.7) and the lowest for Bozola in Bamako district (0.5). Contrary the known information on the high content and distribution of B. in soils, the agricultural soils of Mali contain few Bt strains, confirmed by the low Bt index obtained

Developmental Stability: A Major Role for Cyclin G in Drosophila melanogaster

Morphological consistency in metazoans is remarkable given the pervasive occurrence of genetic variation, environmental effects, and developmental noise. Developmental stability, the ability to reduce developmental noise, is a fundamental property of multicellular organisms, yet its genetic bases remains elusive. Imperfect bilateral symmetry, or fluctuating asymmetry, is commonly used to estimate developmental stability. We observed that Drosophila melanogaster overexpressing Cyclin G (CycG) exhibit wing asymmetry clearly detectable by sight. Quantification of wing size and shape using geometric morphometrics reveals that this asymmetry is a genuine—but extreme—fluctuating asymmetry. Overexpression of CycG indeed leads to a 40-fold increase of wing fluctuating asymmetry, which is an unprecedented effect, for any organ and in any animal model, either in wild populations or mutants. This asymmetry effect is not restricted to wings, since femur length is affected as well. Inactivating CycG by RNAi also induces fluctuating asymmetry but to a lesser extent. Investigating the cellular bases of the phenotypic effects of CycG deregulation, we found that misregulation of cell size is predominant in asymmetric flies. In particular, the tight negative correlation between cell size and cell number observed in wild-type flies is impaired when CycG is upregulated. Our results highlight the role of CycG in the control of developmental stability in D. melanogaster. Furthermore, they show that wing developmental stability is normally ensured via compensatory processes between cell growth and cell proliferation. We discuss the possible role of CycG as a hub in a genetic network that controls developmental stability

Influence of microenvironment on engraftment of transplanted β-cells

Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number of islets needed to restore glucose homeostasis. Moreover, late dysfunction and death contribute to the poor long-term results of islet transplantation on insulin independence. Studies in recent years have identified early and late challenges for transplanted pancreatic islets, including an instant blood-mediated inflammatory reaction when exposing human islets to the blood microenvironment in the portal vein and the low oxygenated milieu of islets transplanted into the liver. Poor revascularization of remaining intact islets combined with severe changes in the gene expression of islets transplanted into the liver contributes to late dysfunction. Strategies to overcome these hurdles have been developed, and some of these interventions are now even tested in clinical trials providing a hope to improve results in clinical islet transplantation. In parallel, experimental and clinical studies have, based on the identified problems with the liver site, evaluated the possibility of change of implantation organ in order to improve the results. Site-specific differences clearly exist in the engraftment of transplanted islets, and a more thorough characterization of alternative locations is needed. New strategies with modifications of islet microenvironment with cells and growth factors adhered to the islet surface or in a surrounding matrix could be designed to intervene with site-specific hurdles and provide possibilities to improve future results of islet transplantation

Effect of Exenatide on Gastric Emptying and Graft Survival in Islet Allograft Recipients

OBJECTIVE: To evaluate the effect of exenatide on gastric emptying and long-term metabolic control. METHODS: Ten islet allograft recipients treated with exenatide up to 4 years. Data from a mixed meal test with (MMT+) versus without (MMT−) administration of exenatide before boost ingestion were analyzed at 6, 12, 24, 36, or 48 months after initiation of exenatide treatment. None of the subjects were symptomatic for gastroparesis before or during the study. The c-peptide, acetaminophen absorption and glucose responses to MMT were analyzed by Student t test and analysis of variance. RESULTS: Average exenatide dose was 12.75 ± 9.46 μg/dL. The MMT subjects included two groups those with acetaminophen peak ≤120 minutes (“good gastric emptying; n = 4”) versus those with an acetaminophen peak ≥180 minutes (“delayed gastric emptying”). Among the MMT+, acetaminophen absorption was the same in both groups (P = .27). Up to 48 months exenatide delayed time to peak of glucose, c-peptide, and acetaminophen as well as suppressed the glucagon response to MMT mean peak: 70.89 ± 12.45 versus 43.24 ± 4.67. The mean values of c-peptide and glucose responses to MMT were not significantly different. CONCLUSIONS: Long-term exenatide administration up to 4 years was safe in islet transplant recipients, even in the presence of delayed gastric emptying. The effects of exenatide were acute and reversible when the agent was withdrawn. The main difficulty with the use of exenatide in islet transplant subjects is their poor tolerability, although the physiological effects are clearly evident even at low doses. Approximately 63% of total subjects under exenatide treatment discontinued the drug due to nausea and vomiting. The use of new GLP1 analogs with longer half lives and fewer side effects may help to attain higher GLP1 levels, therefore improving islet function and survival

Taenia-solium – inhibition of spontaneous evagination of cysticerci by the host inflammatory capsule

The effect of the host's inflammatory capsule or of physical restraint on the spontaneous evagination capacity of Taenia solium cysticerci was evaluated. Parasites obtained from infected pig muscle, in which the surrounding inflammatory capsule was not eliminated, were unable to evaginate spontaneously after 12 or 60 h of culture. This phenomenon was not abolished when the capsule was eliminated and the parasites were cultured in semi-solid agar or in liquid medium

Efficacy and safety of secondary prophylactic vs. on-demand sucrose-formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover study

Background: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. Objective: To compare the effects of secondary prophylaxis with on-demand sucrose-formulated recombinant factor VIII (rFVIII-FS) therapy in severe hemophilia A. Patients and methods: This open-label study included patients aged 30– 45 years with factor VIII (FVIII) coagulant activity < 1 IU dL)1 who were using on-demand FVIII treatment. Patients were treated with rFVIII-FS on demand for 6 months, followed by 7 months prophylaxis (20–40 IU kg)1, three times perweek, with the first month considered a run-in). The primary endpoint was the number of hemarthroses. Results: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25–75%) number of joint bleeds decreased significantly with prophylaxis [0 (0–3)] vs. on-demand [15 (11–26); P < 0.001] therapy. The number of all bleeds was 0 (0–3) vs. 20.5 (14–37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3–39)] compared with on-demand [25 (4–46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2–3 days after the last infusion. Median 48-h and 72-h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL)1, respectively. Treatment was well tolerated, and no inhibitor formation was observed. Conclusion: Secondary prophylaxis with rFVIII-FS significantly reduced the frequency of hemarthroses compared with on-demand therapy in adult patients with severe hemophilia A