Pathological and magnetic resonance imaging findings in a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy and evaluate the magnetic resonance imaging (MRI) manifestations and pathological findings.</p><p><b>METHODS</b>Six neonatal (1-3 days old) Tibet minipigs were randomized into model group (n=4) and control group (n=2). In model group, hypoxic-ischemic encephalopathy was induced by surgical ligation of the bilateral carotid artery followedimmediately by hypoxic exposure in a hypoxia chamber for 1 h. ESWAN was performed at 2 h, 24 h, 3 days and 5 days after induction of HIE or at 2 h after sham surgery in the control animals to evaluate the brain damage. Conventional MRI scans (T2FLAIR, T2WI, and DWI) were also performed at 24 h after the modeling.</p><p><b>RESULTS</b>In the neostriatum, values of T(2)*-weighted MRI increased and reached the peak level at 3 days post-injury (P<0.05). Subcortical white matter T(2)* values reached the peak level at 24 h (P<0.05). Neostriatum R(2)* values were at the lowest level at 3 days (P<0.05). Magnitude values were significantly increased after the model establishment (P<0.05). DWI showed multiple mild focal high signals in the bifrontal subcortical white matter and bilateral neostriatum; T2FLAIR showed slightly increased signal; T2WI showed no obvious abnormalities. SWI showed dilated medulla veins adjacent to the bilateral lateral ventricles and basal ganglia. In the early stage of HIE, brain pathologies were characterized mainly by edema and venous congestion with occasional focal necrosis and hemosiderin deposition.</p><p><b>CONCLUSION</b>ESWAN sequence is capable of detecting bleeding and brain edema, and T(2)*, R(2)*, and magnitude values can be used to estimate the changes of brain damage following HIE.</p>

A study of reference intervals for serum thyrotropin and thyroid hormones during the neonatal period for the healthy term newborns in Suqian / 中华内分泌代谢杂志

Objective To establish thyrotropin( TSH) and thyroid hormones reference ranges during the neonatal period for the healthy term newborns in Suqian. Methods Blood samples from a heel-prick were collected from 500 healthy newborns 72 hours after birth to determine the level of TSH. 200 healthy newborns were chosen to determine the levels of serum TSH and thyroid hormones on the 14th day of life, and then compared with the results from 120 healthy adults. Results The reference range of TSH at 72 hours after birth was 0. 46-6. 59 mIU/ L. The reference ranges of TT3 , TT4 , TSH, FT3 , FT4 on the 14th day of life were 1. 10-2. 62 nmol/ L, 81. 10-158. 28 nmol/ L, 0. 83-6. 39 mIU/ L, 3. 76-6. 66 pmol/ L, and 10. 67-22. 27 pmol/ L, respectively. There was no significant difference in the interval of TSH between newborns and adluts, whereas there were significant difference in the intervals of TT3 , TT4 , FT3 , and FT4 between the two groups. Conclusions The establishment of TSH and thyroid hormone reference ranges during the neonatal period for the healthy term newborns could improve our understanding of the thyroid function during the neonatal period for the healthy term newborns, and our data suggests lowing the initiatory screening cut-off point of congential hypothyroidism.

Lung adenocarcinoma stem cell phenotypes and their correlation with patient prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the cancer stem cells and to evaluate their prognostic implication in patients with lung adenocarcinoma.</p><p><b>METHODS</b>Three phenotypic markers of cancer stem cells (SP-C, CCSP and OCT4) in lung adenocarcinoma were detected by immunofluorecence staining. The correlation among the clinicopathological parameters and phenotypes of cancer stem cells as well as survival were analyzed by Cox proportional hazard method.</p><p><b>RESULTS</b>Of the 57 cases, cancer stem cells were detected in 52, including OCT4(+) bronchioloalveolar stem cell (BASC) phenotype (SP-C(+) CCSP(+) OCT4(+)) in 40 cases and OCT4(-) BASC phenotype (SP-C(+) CCSP(+) OCT4(-)) in 12 cases. Statistical analysis revealed that the phenotype of cancer stem cells was related with the cellular differentiation, i.e. the OCT4(+) BASC phenotype occurred more frequently in the well-differentiated tumors, while the OCT4(-) BASC phenotype usually presented in most of the poorly-differentiated ones. Cox analysis showed that the OCT4(+) BASC phenotype was one of prognostic factors.</p><p><b>CONCLUSION</b>The lung adenocarcinoma stem cells have phenotypic features of bronchioalveolar stem cells (SP-C(+) CCSP(+)). The expression of self-renewal regulatory gene OCT4 in these cells indicates an aggressive nature and unfavorable prognosis.</p>

Isolation and identification of human lung adenocarcinoma stem cells / 肿瘤

Objective: To isolate and characterize the highly tumorigenic cancer stem cells with stem cell features from the established human lung adenocarcinoma cell lines. Methods: The cell subtypes were separated by magnetic activated cell sorting (MACS) technique. The stem cell-related markers on the isolated cells were detected by using flow cytometry and RT-PCR. The tumorigenic potent of the isolated cells was evaluated via the transplantation into NOD-SCID mice. Results: A novel cell subtype was identified in A 549 and SPC-A1 lung adenocarcinoma cell lines. These cells were characterized as a phenotype of CD 24+ IGF-1R+, possessed the property of high invasiveness and high tumorigenesis. Tumor could be induced in NOD-SCID mice by transplantation of CD 24+IGF-1R+ cells at 100 cells per mouse. The tumorigenicity of CD 24+IGF-1R+ cells had 1000-fold increase compared with CD 24-IGF-1R- cells. In addition, the CD 24+IGF-1R+ cells expressed embryonic stem cell markers (OCT 4 and Bmi-1) and lung stem cell markers (CCSP, SP-C, TTF-1, and Gremlin), suggesting that they had the features identical to the bronchioalveolar stem cells (BASC) in the lung of mice. These cells also exhibited autonomous growth features and could be cultured in serum-free conditions for a long time. Conclusion: The CD 24+IGF-1R+ cells in human lung adeocarcinoma belongs to the BASC-like cancer stem cells.

Analysis of EGFR mutations in 176 cases of non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the incidence and profile of mutations in epidermal growth factor receptor (EGFR) in Chinese patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 176 cases of NSCLC tissue was enrolled in this study, among which 123 normal lung samples were also included. The tissue DNA was extracted and the EGFR gene in exon 19 to 21 was subjected for PCR amplification and direct sequencing.</p><p><b>RESULTS</b>The EGFR gene in exon 19-21 was of wild type in all normal lung tissues detected. Mutations were found in 57 cases of 176 lung cancer samples, with an incidence of 32. 4%. Mutations were mainly detected in the exon 19 (37/57 cases, 64. 9% ) and exon 21 (18/57 cases, 31. 6% ) , while that in the exon 20 was rare (2/57 cases, 3. 5% ). There were 7 types of EGFR mutation in the exon 19, resulting in the deletion of codon 746 to 753. A missense mutation was detected in exon 20, dealing with codon 789 to 793. The mutation in exon 21 belonged to the single missense substitution in codon 858. The EGFR mutations were more frequent in female patients than male ones, in adenocarcinoma and adenosquamous cell carcinoma versus cancer of other histologies.</p><p><b>CONCLUSION</b>EGFR mutation is a tumor-specific somatic abnormality. Some one third of Chinese NSCLC tumors harbor EGFR mutations, especially in exons 19 and 21. These mutations are more frequently detected in female, adenocarcinoma and adenosquamous cell carcinoma.</p>

Implication of micrometastatic cancer cells in the peripheral blood on prognosis of non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the relationship of micrometastatic cancer cells in the blood and prognosis of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Blood samples were collected from peripheral vein perioperatively and from the pulmonary vein intraoperatively in NSCLC patients. Cancer cells were detected by flow cytometry, as described previously. The patients were followed up and analyzed statistically.</p><p><b>RESULTS</b>Cancer cells in blood samples were detected in 20 of 58 patients (34.5%). Patients under 57 years of age or with stage III/IV lesions had higher positive findings than those over 57 years or with stage I/II lesions (P = 0.000 and 0.006, respectively). On the basis of 40 month follow-up data, the 2- and 3-year survival rates of patients with positive and negative results were 30.0% vs 20.0%, and 52.6% vs 50.0%, respectively. There was significant difference between the overall survival curves which favored patients with negative findings (P = 0.0291 and 0.0092, respectively).</p><p><b>CONCLUSION</b>This study indicates that cancer cells can be detected in the blood perioperatively from NSCLC patients which means poor prognosis.</p>

Can tumor uptake Tc-99m MDP ?

Abstract. To explore the mechanism of technetium-99m-methylene diphosphonate (MDP) uptake within tumor through analyze a distribution of Tc-99m MDP in mice bearing tumor cell lines. Methods: The uptake of Tc-99m MDP was analyzed in seven human tumor cell lines ( SPC-A1 adenocarcinoma of lung cancer, Bcap-37 Breast cancer, T-24 Bladder cancer, SKOV3 Ovary carcinoma, Hela-229 Cervical carcinoma, SCI-OS Osteosarcoma, SCI-375 Melanoma) and mouse Lewis lung cancer cell line. They were transplanted into athymic mice, SCID nude mice and C57BL/6 mice, respectively. Approximately 10(6) cells of each cell line were injected subcutaneously into a right chest of mouse. After 4&5 weeks, the Tc-99m MDP scintigraphy were determined 6 hours after tail vein injection of 74MBq in 0.05ml every mouse. Result: Biodistribution and tumor uptake MDP was different in the various cell types investigated. According to the RegionRatio program of Siemens Power Macintosh 9500 Computer System, region of interests (RIOs) placed on a small part of the tumor and horizontal copied to left background (T/B) and thoracic spine (T/N) of mice in Tc-99m MDP imaging. The average cpm/pixel ratios were calculated by standardized uptake measure (SUM) and determined the tumor-positive value (T/B) greater than or equal to 1.2. T/B of cell lines were sorted from higher to lower as follows: SCI-OS, Lewis, SKOV3, SCI-375, T-24, SPC-A1, Bcap-37, Hela-229. T/N: SCI-OS, SKOV3, T-24, SCI-375, Lewis, SPC-A1, Bcap-37, Hela-229. The biodistribution data of 99Tcm-MDP in SPC-A1 tumor-bearing BALB/c nude mice were given as ID/g and represent the meansñSD (n=13) in 30 hours after injection of Tc-99m MDP. ID/g of major tissue were sorted from higher to lower as follows: thoracic spine, lumbar, ribs, kidneys, the center of tumor, the ulcer of tumor, the surrounding of tumor, lymph node, blood, lungs, heart, liver. Conclusions: Most of tumor can uptake Tc-99m MDP including human adenocarcinoma. The uptake rate in the center tissue of tumor is higher than other part of tumor. The uptake rate of tumor is higher than non-skeletal tissue unless kidneys. It maybe connected with necrosis or calcification of tumor. Calcium and phosphorus ions were seen frequently in larger tumor. Not only it was caused by fibrous scar and/or surrounding tissues of granuloma but also intra-tumor coagulation and liquefaction necrosis