Cutaneous T-cell lymphomas (CTCL) are a group of skin neoplasms that originate from T lymphocytes and are difficult to treat in advanced stages. The present study is aimed at the identification of tumor-specific antigens from a human testis cDNA library using human sera known as the SEREX (serological identification of recombinantly expressed genes) approach. A cDNA library from normal testicle tissue was prepared and approximately 2 million recombinants were screened with sera from Sézary Syndrome and Mycosis fungoides patients. A total of 28 positive clones belonging to 15 different genes/ORFs were identified, including five hitherto unknown sequences. Whereas control sera did not react with most clones, 11–71% sera from CTCL patients were reactive against the identified clones. Expression analysis on 28 normal control and 17 CTCL tissues by reverse transcription–PCR (RT-PCR) and Northern blotting revealed seven ubiquitously distributed antigens, six differentially expressed antigens (several normal tissues were positive), and two tumor-specific antigens that were expressed only in testis and tumor tissues: ( i ) A SCP-1-like sequence, which has already been detected in various tumors, has been found in one CTCL tumor and four sera of CTCL patients reacted with various SCP-1-like clones and ( ii ) a new sequence named cTAGE-1 (CTCL-associated antigen 1) was detected in 35% of CTCL tumor tissues and sera of 6/18 patients reacted with this clone. The present study unravels CTCL-associated antigens independent of the T-cell receptor. The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL.
The ZRKL of the DDG for the first time presents epidemiologic data from Germany, allowing comparison with other nations for the study of etio-logical factors and socioeconomic influences. Further, the ZRKL supports the development of uniform and quality-oriented diagnostic criteria and therapeutic options. Finally, the ZRKL provides a foundation for future intensive study of clinical and scientific questions regarding cutaneous T- and B-cell lymphomas.
Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin.
A higher incidence of stomach cancer in ABO blood type A individuals than in those with blood type O has been known for a long time. We studied this association in relation to Helicobacter pylori (Hp) of different cagA status. For this study we used baseline gastric histopathology data and DNAs from frozen gastric biopsies of 2077 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela. We analyzed 6 single nucleotide polymorphisms in the ABO gene and we assessed the presence of the Hp cagA gene. Odds ratios for risk of advanced precancerous gastric lesions were calculated using individuals with normal gastric epithelium or non-atrophic gastritis as a reference. Among individuals carrying a cagA negative Hp infection or no Hp infection, those with blood type A had a lower risk of intestinal metaplasia and dysplasia than those with blood type O (OR=0.60; 95% CI 0.38-0.94). In carriers of cagA positive Hp strains, individuals with blood type A had a higher risk of intestinal metaplasia or dysplasia than those with blood type O (OR=1.42, 95% CI 1.09-1.86) and a higher risk if compared with subjects carrying cagA− strain and non-A blood group (OR=3.82, 95%CI=2.80-5.20). The interaction between Hp cagA status and blood type was statistically significant (P=0.0006). We showed that SNPs in the ABO gene, predictive of ABO blood groups, are associated with risk of advanced precancerous gastric lesions in individuals infected with Hp, but the assessment of the risk is strictly dependent on cagA status.
BackgroundGenetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut.MethodsWe performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries.ResultsWe did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071).ConclusionsOur data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts.Electronic supplementary materialThe online version of this article (10.1186/s12876-017-0659-9) contains supplementary material, which is available to authorized users.
Die Acne inversa ist durch eine chronisch-rezidivierende suppurative Entzündung der Haut charakterisiert. Sie imponiert durch eine Vielzahl von klinischen Erscheinungsbildern, die vom Frühstadium mit Riesenkomedonen über entzündliche Papeln und Knoten bis zu Abszessen und ausgedehnten abszedierenden Fistelgängen mit Narbenbildungen reichen. Unbehandelt verläuft die Acne inversa chronisch-progredient und kann bei den Betroffenen aufgrund der Schmerzen, Bewegungseinschränkungen, dermalen Kontrakturen und hämorrhagisch-eitrigen Sekretabsonderungen aus den betroffenen Arealen zur psychosozialen und gesellschaftlichen Isolation führen. Um den Patienten jahrelanges Leiden und Komplikationen zu ersparen, sind eine frühzeitige Diagnosestellung und vollständige chirurgische Exzision der pathologisch veränderten Haut erforderlich.Pharmakotherapeutische Maßnahmen haben dabei weitestgehend adjuvanten Charakter. AbstractAcne inversa is characterized by chronic, recurrent, suppurative inflammation of the skin. The variety of clinical pictures is impressive, ranging from an early stage with giant comedones to inflammatory papules and nodules up to recurrent abscesses and extensive draining sinus with scar formation. Left untreated, acne inversa runs a chronic, progressive course and can lead those afflicted into psychosocial and social isolation due to the pain, limitation of mobility,dermal contractures, and hemorrhagic and purulent secretions from the affected areas.To spare the patients long-lasting suffering and complications, early diagnosis and complete surgical excision of the altered skin are indispensable. Pharmacotherapeutic measures do not prevent progression of the disease and play an adjuvant role.
Helicobacter pylori (Hp) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. increased virulence in Hp isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagpAi). We analyzed the microvariants in cagpAi genes with the hypothesis that they may play an important role in determining Hp virulence. We tested DnAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (cG, n = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagpAi genes from Latin American Western Hp strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.Gastric cancer has the third highest mortality rate and the fifth highest incidence worldwide 1 . The two regions of the world with highest mortality rate for gastric cancer are Asia and Latin America accounting for almost two thirds of all gastric cancer deaths 2 . Within the US, ethnic minorities, e.g., Asians, Blacks, Hispanics and Native Americans, experience an incidence almost twice as high as non-Hispanic Whites 3 . Some Asian countries, such as Japan, have nation-wide screening programs for early detection of gastric cancer, whereas most other high-risk countries, such as Latin American countries, do not have such programs, nor does the US for ethnic minorities 4-6 . Although Helicobacter pylori (HP) is an established cause of gastric cancer 7 , eradication of HP in general asymptomatic populations has not been advised, because of the large number of persons already infected in high risk populations (>90%), high reinfection rates in endemic areas 8 , antibiotic resistance, high cost of the treatment 9 and the increased risk of esophageal cancer associated with HP-negative/eradicated individuals 10-12 . Thus, new strategies for gastric cancer prevention are warranted and may help reduce health disparities, mainly in the most affected and underdeveloped regions of the world 13 . All considered identification of new HP variants potentially useful to predict gastric cancer risk will be invaluable not only for vaccine development, but also to target antibiotic treatment to high-risk individuals.HP has a remarkably high level of genetic diversity due to rec...
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