238 research outputs found
The clinical utility of testicular cancer risk loci
Three recent genome-wide association studies of testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1. The calculated per-allele odds ratio for variants in the region of KITLG is the highest reported for any malignancy so far. These findings are in agreement with epidemiological data indicating that testicular cancer has a higher heritability than most other cancers. Here, we discuss the question of whether the newly identified risk polymorphisms can be used to guide patient care
Vitamin D Deficiency in Obese Children and Its Relationship to Insulin Resistance and Adipokines
Low-serum concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with insulin resistance in adults. Less data are available in pediatric populations. Serum 25(OH)D serum concentrations were assessed in 125 obese and 31 nonobese children (age 11.9 ± 2.7 y, range 6–16 y, 49% male) living in Bonn, Germany. The relationship between 25(OH)D, measured by liquid chromatography-tandem mass spectrometry, and measures of insulin sensitivity and adipokines adiponectin and resistin were analyzed. Seventy-six % of subjects were 25(OH)D deficient (<20 ng/mL). Higher insulin, homeostasis model assessment-insulin resistance (HOMA-IR r = −0.269, P = 0.023), and hemoglobin A1c (HbA1c) as well as lower quantitative insulin-sensitivity check index (QUICKI r = 0.264, P = 0.030) values were found in obese children with lower 25(OH)D concentrations even after adjustment for gender, age, and body mass index. Furthermore, 25(OH)D correlated significantly with adiponectin, but not with resistin. Our results suggest that hypovitaminosis D is a risk factor for developing insulin resistance independent of adiposity
Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector molecules such as activation-induced cytidine deaminase and uracil N-glycosylase. We report a new form of B cell–intrinsic CSR deficiency found in three patients with deleterious, homozygous mutations in the gene encoding the PMS2 component of the mismatch repair machinery. CSR was found partially defective in vivo and markedly impaired in vitro. It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation
The Lantern Vol. 22, No. 2, March 1954
• Checkmate • An Impression • The Excavation at Ursinus College • Chant d\u27Antomne • Impasse At Dick\u27s Dell • The Master\u27s Hands • Wanderer • The Wiser Tongue • Time Passing • Achoo! Or It\u27s All In Your Head • From The Tower Windowhttps://digitalcommons.ursinus.edu/lantern/1062/thumbnail.jp
Epidemiology and Characteristics of Gastric Carcinoma in Childhood : An Analysis of Data from Population-Based and Clinical Cancer Registries
(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is
known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This
analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in
childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000
and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER)
and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed
for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric
carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for
diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in
adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded
staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered,
63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma
were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations
and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly
decreased immunoglobulin concentrations. All four patients in whom complete resection was
achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or
immunodeficiency appears to promote the development of gastric carcinoma in childhood. While
patients with localized disease stages have a good chance of achieving durable remission through
complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need
to develop new strategies such as mutation-guided treatments
Maleimide-functionalised platinum(IV) complexes as synthetic platform for targeted drug delivery
Maleimide-functionalised Pt(IV) complexes with highly
selective binding properties to thiol groups were synthesised as precursors for binding of thiol-containing tumour
targeting molecules like human serum albumi
Research on Rare Diseases in Germany - Cancer Predisposition Syndrome Registry
Background: Cancer predisposition syndromes (CPS) are rare diseases that are associated with an increased risk of cancer due to genetic alterations. At least 8 % of all cases of childhood cancer are attributable to CPS. The CPS registry was launched in 2017 to learn more about CPS and to improve the care to those afflicted by these diseases.
Methods: This is an internationally networked registry with associated accompanying studies that investigate cancer risks and spectra, the possibilities of cancer prevention, early detection and therapy.
Results: For several of these syndromes, new insights into the cancer risks and cancer types as well as factors modifying cancer risk have been gained. In addition, experimental, psycho-oncological, preclinical and clinical studies were initiated.
Conclusions: The CPS registry is an example of how progress can be made within a short period of time to the benefit of individuals with rare diseases through systematic data collection and research
Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR).
BACKGROUND
Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance.
METHODS
Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed.
RESULTS
Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively.
CONCLUSION
Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups
Molecular complete remission following combination treatment of daratumumab and venetoclax in an adolescent with relapsed mixed phenotype acute leukemia
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