Interleukin-22 Is Frequently Expressed in Small- and Large-Cell Lung Cancer and Promotes Growth in Chemotherapy-Resistant Cancer Cells

Introduction: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients. Methods: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay. Results: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed. Conclusion: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype

Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome

Abstract Background RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer. Methods RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data. Results While nuclear RBM3 expression was always high in benign esophageal epithelium, high RBM3 expression was only detectable in 66.4% of interpretable EACs and 59.3% of ESCCs. Decreased RBM3 expression was linked to a subset of EACs with advanced UICC stage and presence of distant metastasis (P = 0.0031 and P = 0.0024). In ESCC, decreased RBM3 expression was associated with advanced UICC stage, high tumor stage, and positive lymph node status (P = 0.0213, P = 0.0061, and P = 0.0192). However, RBM3 expression was largely unrelated to survival of patients with esophageal cancer (EAC: P = 0.212 and ESCC: P = 0.5992). Conclusions In summary, the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis

Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer

Abstract Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p). Results ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status (p < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence (p < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability. Conclusion The results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors

The charcoal trap: Miombo forests and the energy needs of people

<p>Abstract</p> <p>Background</p> <p>This study evaluates the carbon dioxide and other greenhouse gas fluxes to the atmosphere resulting from charcoal production in Zambia. It combines new biomass and flux data from a study, that was conducted in a <it>miombo </it>woodland within the Kataba Forest Reserve in the Western Province of Zambia, with data from other studies.</p> <p>Results</p> <p>The measurements at Kataba compared protected area (3 plots) with a highly disturbed plot outside the forest reserve and showed considerably reduced biomass after logging for charcoal production. The average aboveground biomass content of the reserve (Plots 2-4) was around 150 t ha^-1, while the disturbed plot only contained 24 t ha^-1. Soil carbon was not reduced significantly in the disturbed plot. Two years of eddy covariance measurements resulted in net ecosystem exchange values of -17 ± 31 g C m^-2y^-1, in the first and 90 ± 16 g C m^-2in the second year. Thus, on the basis of these two years of measurement, there is no evidence that the <it>miombo </it>woodland at Kataba represents a present-day carbon sink. At the country level, it is likely that deforestation for charcoal production currently leads to a per capita emission rate of 2 - 3 t CO₂y^-1. This is due to poor forest regeneration, although the resilience of <it>miombo </it>woodlands is high. Better post-harvest management could change this situation.</p> <p>Conclusions</p> <p>We argue that protection of <it>miombo </it>woodlands has to account for the energy demands of the population. The production at national scale that we estimated converts into 10,000 - 15,000 GWh y^-1of energy in the charcoal. The term "Charcoal Trap" we introduce, describes the fact that this energy supply has to be substituted when woodlands are protected. One possible solution, a shift in energy supply from charcoal to electricity, would reduce the pressure of forests but requires high investments into grid and power generation. Since Zambia currently cannot generate this money by itself, the country will remain locked in the charcoal trap such as many other of its African neighbours. The question arises whether and how money and technology transfer to increase regenerative electrical power generation should become part of a post-Kyoto process. Furthermore, better inventory data are urgently required to improve knowledge about the current state of the woodland usage and recovery. Net greenhouse gas emissions could be reduced substantially by improving the post-harvest management, charcoal production technology and/or providing alternative energy supply.</p

Presence of adenovirus species C in infiltrating lymphocytes of human sarcoma.

Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation

Pure Testicular Seminoma Relapsing Late with Somatic Type Malignancy

Background. Somatic type malignancy (STM) occurs in 2% of all germ cell tumours (GCTs). The prognosis is unfavourable and the origin is poorly understood. Pathogenetic hypotheses involve direct transformation of teratoma, origin from totipotent cancer cells, or derivation from yolk sac tumour elements. Case Presentation. A 31-year-old patient was cured from testicular seminoma clinical stage IIc by orchiectomy and cisplatin-based chemotherapy. Nine years later, he experienced a late relapse with a mass sized 5×6 cm located at the former metastatic site. As no remission occurred after chemotherapy with three cycles of cisplatin, ifosfamide and etoposide, the mass was surgically resected. Histologically, the specimen consisted of neurofibroma with areas of malignant peripheral nerve sheath tumour and spots with mature bone formation. FISH analysis disclosed isochromosome 12p in the majority of evaluated cells suggesting somatic type malignancy (STM) of GCT. The patient is well 1 year after surgery. Conclusion. The pathogenesis of this STM remains enigmatic. The origin from GCT was evidenced by documentation of isochromosome 12p. Unrecognized teratomatous elements in the primary and totipotent cancer cells surviving the first chemotherapy could be hypothesized to represent the origin. STM developing from seminoma cells would be another novel hypothesis

qRT-PCR and sequencing analysis of adenovirus DNA in human sarcomas.

<p>All PCR positive sarcoma specimens are shown. In samples 32 and 42 the laboratory strain with a deletion in the E3 region was detected. In sample 62 a sequence identical for type 2 and type 6 has been identified. GIST: gastro intestinal stroma tumors.</p

Typing of adenovirus strains present in human sarcoma specimens.

<p>E1A has been amplified by nested PCR in species C positive samples. A) A detailed scheme shows the binding sites of the oligonucleotides for the first and second round of the nested PCR. B) 531bps of the E1A gene have been sequenced from 7 different samples. A part of the sequences investigated are depicted in an alignment with two reference GenBank sequences of HAdV-5 (NCBI acc. no.: AY339865) and HAdV-6 (NCBI acc. no.: HQ413315.1).</p

HAdV copy numbers in human sarcomas detected by qRT-PCR.

<p>qRT-PCR was performed for the hexon gene of HAdV and for beta-2-microglobulin, B2M (a single human house-keeping gene). The calculation of the viral copies is related to the copy number of the house-keeping gene for each specimen. The virus copy numbers per 10³ cells are shown for 4 leiomyosarcoma (Lei), 7 liposarcoma (Lip) and one GIST (gastro intestinal stroma tumor).</p