Bioinformatics analysis of HLA-A2 restricted neoantigen epitopes in breast cancer / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To screen candidate epitopes of breast cancer HLA-A2 restrictive neoantigen and to identify high frequency mutation sites in breast cancer neoantigen by using bioinformatics method. Methods: NCBI and GDC databases were used to search missense mutation sites formed by single nucleotide mutation in breast cancer among reported literatures and sequencing data. The new antigen epitopes were predicted by HLA-A2 antigen epitope prediction website BIMAS, SYFPEITHI and artificial neural networkbased NetMHC4.0, and the epitopes with TAP binding power less than Intermediate were eliminated. The candidate epitopes were prioritized by mutation frequency and prediction results. Results: A total of 17 high-frequency mutation genes, including BTLA, ERBB2 and NBPF12 etc, were screened by the above-mentioned methods, and a total of 26 neoantigen epitopes were identified. The binding power of epitopes predicted using BIMAS and SYFPEITHI showed great difference (P<0.05), epitopes in high priority as GSTP1 (A114V , mutation frequency of 5.94%) and BRCA2 (N991H, mutation frequency of 5.40%) etc, were expected to be candidate neo-antigen epitopes; however, their mutation frequency was relatively too low to achieve“universal use” . The possibility of these epitopes used as general breast cancer neo-antigen epitopes is less likely. Conclusion: The common mutation frequency of breast cancer is lower than that of other tumors; it ’s difficult to find“universal”new antigen epitopes of breast cancer; the individualized neoantigen vaccine may be of more promise, which needs further research.

Hypercalcemia appeared in a patient with glucagonoma treated with octreotide acetate long-acting release / 中国医学科学杂志(英文版)

PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

Effect of long term glucocorticoid treatment on human growth hormone secretion in children and adolescents and the safety and effectiveness of recombinant human growth hormone treatment / 中国医学科学院学报

<p><b>OBJECTIVE</b>Long term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment.</p><p><b>METHODS</b>Twelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved.</p><p><b>RESULTS</b>The growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (P<0.05), and then to 6.9∓0.4cm/year one year later.</p><p><b>CONCLUSIONS</b>The long-term glucocorticoid treatment can decrease the hGH secretion, and thus leads to short stature and agenesis. However, the rhGH replacement can safely and effectively improve growth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.</p>

Growth and development of adolescent patients with Cushing's syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To elucidate the growth and development of patients with Cushing's syndrome (CS) in adolescence.</p><p><b>METHODS</b>We analyzed the clinical data of 19 patients aged under 18 with CS. We divided the patients into two groups according to the height at diagnosis. The patients under the 3rd percentile were in the short stature group (n=12), and the others in the non-short stature group (n=7). The intergroup differences in disease course, age of onset, and 24-hour urinary free cortisol were analyzed.</p><p><b>RESULTS</b>The median age at diagnosis was 13 years. The median disease course was 0.9 years. All those patients presented with typical clinical characteristics of CS. Twelve cases (63.2%) were in short stature group. The disease course of the short stature group was found significantly longer than that of the non-short stature group [(2.7∓1.7) years vs. (0.8∓0.6) years, P=0.013], but no significant difference was found in the age of onset (P=0.530) or 24-hour urinary free cortisol (P=0.919) between the two groups.</p><p><b>CONCLUSIONS</b>The data suggest that short stature is common in adolescent CS patients. The growth delay may be correlated to the disease course of CS.</p>

Value of 18F fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in diagnosis and localization of Cushing's disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the value of [18F]fluoro-2-deoxy-D-glucose(18 FDG) positron emission tomography and computer tomography (PET/CT) in the qualitative diagnosis and localization of Cushing's disease.</p><p><b>METHODS</b>Totally 12 patients underwent transsphenoidal adenomectomy and were histopathologically proven to be with Cushing's disease. 18FDG PET/CT whole-body and brain scannings were performed preoperatively; meanwhile, magnetic resonance imaging (MRI) and 99mTc-octreotide examination were done in all 12 cases, and inferior petrosal sinus sampling (IPSS) were done in 6 patients.</p><p><b>RESULTS</b>The sensitivity of 18FDG in diagnosing Cushing's disease was 91.6% (11/12), but MRI was 66.7%(8/12). For the 6 patients who performed IPSS, 5 of them was diagnosed to be with Cushing's disease, and only 50% (3/6) were localized correctly in the pituitary gland.</p><p><b>CONCLUSIONS</b>18FDG PET/CT whole-body scan can exclude ectopic adrenocorticotropin-secreting tumors and localize the pituitary lesions with higher accuracy than MRI. Therefore, it is useful for suspected Cushing's disease, especially for patients their MRI and IPSS have negative or paradoxical results.</p>

Value of brain magnetic resonance imaging and tumor markers in the diagnosis and treatment of intracranial germinoma in children / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the role of brain magnetic resonance imaging (MRI) and tumor markers in the cerebral spinal fluid (CSF) and serum in the diagnosis and treatment of intracranial germinoma in children.</p><p><b>METHODS</b>Totally 5 children (3 girls and 2 boys) who were treated in our hospital between January 2009 and December 2010 due to central diabetes insipidus. All patients received contrast-enhanced brain MRI at presentation and during each follow-up: meanwhile, their anterior pituitary hormones and tumor markers including human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were also determined.</p><p><b>RESULTS</b>Three patients presented without prior evaluation, and two patients were referred to our hospital due to exaggerated disease of unknown cause. Their ages at presentation ranged from 8 years to 12 years 1 month, and the duration of symptoms at presentation was between 1 month to 78 months. All of them had polyuria and polydipsia at presentation. Except one child, the other 4 patients had growth retardation and failure in initiation of puberty. Although the growth rate and puberty development were normal during the 2-year follow-up for the excepted child, all child experienced anterior pituitary hypofunction and an increased concentration of plasma prolactin after the lesion became enlarged. Three patients had cerebral hernia, which presented in 18, 24, and 78 months, respectively. In three patients, brain MRI at presentation showed isolated pituitary stalk thickening, which further developed into massive tumor in the hypothalamus pituitary region 18-22 months later; in the remaining two patients, large brain tumor was found via MRI at their first presentations. In all five patients, the posterior pituitary gland (bright spot) disappeared on T1-weighted MRI images. CSF hCG elevated in all five patients, and serum hCG increased in four patients; the level of hCG varied with the mass size of tumor. Serum and CSF AFP increased in only one patient.</p><p><b>CONCLUSIONS</b>Patients with idiopathic central diabetes insipidus must be closely followed to identify the etiology, especially when anterior pituitary hormone deficiencies are detected. For patients with normal brain MRI results or simply isolated pituitary stalk thickening at presentation, the changes of serial contrast-enhanced brain MRI should be observed during follow-up to ensure the early detection of an evolving occult hypothalamic-stalk lesion. Determination of CSF hCG at the first presentation may be useful, because an increased CSF level of hCG precedes MRI abnormalities.</p>