[Application of diffusion-weighted magnetic resonance imaging in evaluating the efficacy of radiotherapy and chemotherapy for esophageal cancer].

This study was a prospective single arm trial conducted in Zhejiang Jinhua Guangfu hospital from February 2018 to June 2020. A total of 39 patients (32 males and 7 females) with esophageal cancer, aged from 44 to 82 (69±9) years were enrolled. Diffusion weighted magnetic resonance imaging(MR-DWI) was implemented to evaluate the changes of apparent diffusion coefficient(ADC) value before and after chemoradiotherapy. The results showed that the ADC value after chemoradiotherapy was higher than that before treatment[(2.03±0.42)×10⁻³ mm 2/s vs (1.60±0.28)×10⁻³ mm2/s], and there was a positive correlation between the increase of ADC value and the prognosis of patients.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

Microarray gene expression profiling for identifying different responses to radiotherapy and chemoradiotherapy in patients with cervical cancer.

PURPOSE: Cervical cancer, which is treated by radiotherapy (RT) and chemoradiotherapy (CRT), has high morbidity and mortality in women. This study aimed to identify differences in gene response to CRT and RT. MATERIALS AND METHODS: GSE3578 was downloaded from Gene Expression Omnibus including specimens from 20 RT-treated patients and 19 CRT-treated patients. Differentially expressed genes (DEGs) were identified using siggenes package in R. Protein-protein interaction (PPI) network was visualized by cytoscape. MCODE and cytoscape was used separately to mine and construct modules in the PPI network. Transcription factor (TF)-DEG and miRNA-DEG pairs were predicted and then visualized by cytoscape. RESULTS: Total 22 upregulated and 181 downregulated genes were identified in CRT samples. Several functions were enriched for these DEGs. A module involving ZNF449 and ZNF673 was mined from the PPI network of downregulated genes. In the TF-DEG regulatory networks, downregulated GATA3 (which was modulated by SPI) was also a TF, as well as upregulated CDK6 was regulated by several TFs (e.g. GATA3). Hsa-miR-17, hsa-miR-34a, hsa-miR-124, hsa-miR-I185-2-3p, hsa- 1185-1-3p, and hsa-let-7f-2-3p were identified as key miRNAs in the miRNA-DEG regulatory network. Conclu- sion: CRT might cure cervical cancer by acting on those molecules that were more sensitive to CRT than CT.

Association of LncRNA HMlincRNA717 with prognosis in pancreatic cancer.

OBJECTIVE: The aim of this study was to investigate the expression of LncRNA HMlincRNA717 in human pancreatic cancer and its correlation with clinicopathological features PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, HMlincRNA717 expression was detected in primary pancreatic cancer tissues. The correlation of HMlincRNA717 with clinicopathological features and prognosis were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: The expression of HMlincRNA717 was significantly decreased in pancreatic cancer tissues compared with paired adjacent normal tissues (p < 0.01). It was also proved that HMlincRNA717 expression was to be associated with clinical stage (p = 0.001), tumor size (p < 0.001), lymph node metastasis (p = 0.003), and distant metastasis (p < 0.001) in pancreatic cancer patients. Significantly shorter 5-year overall survival (OS) were observed in patients with lower expression of the HMlincRNA717 (p < 0.01). Multivariate analysis showed that decreased HMlincRNA717 expression was a poor independent prognostic factor for pancreatic cancer patients. CONCLUSIONS: Our findings showed that the expression of lncRNA HMlincRNA717 was down-regulated in pancreatic cancer and associated with overall survival, suggesting that HMlincRNA717 could be a potential prognostic biomarker for pancreatic cancer progression.

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in mucosa-associated lymphoid tissue lymphoma of the larynx: a case report and literature review.

Laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, with only 25 cases reported in the literature. This report presents a case of laryngeal MALT lymphoma in a 35-year-old female with a 6-year history of progressively worsening hoarseness. MALT lymphoma was diagnosed based on biopsy and immunohistochemical analysis. The patient received two cycles of cyclophosphamide + epirubicin + vincristine + prednisone (CHOP) chemo therapy, which was ineffective. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) showed (18)F-FDG accumulation in the larynx only and identified stage IE lymphoma. CHOP chemotherapy was terminated and the patient was treated with radiotherapy. After 3 months (total radiation dose 27 Gy), (18)F-FDG PET/CT scan showed that the laryngeal lesion was in complete remission. A review of the literature on the MEDLINE(®)/PubMed(®) databases regarding laryngeal MALT lymphoma and the use of PET/CT found that radiotherapy is the first-line treatment for stage I and II MALT lymphoma.

Compromised perfusion in femoral head in normal rats: distinctive perfusion MRI evidence of contrast washout delay.

OBJECTIVES: The femoral head is prone to osteonecrosis. This study investigated dynamic contrast-enhanced (DCE) MRI contrast washout features of the femoral head and compared the data with data from other bony compartments in normal rats. METHODS: 7-month-old Wistar rats were used. DCE MRI of the right hip (n=18), right knee (n=12) and lumbar spine (n=10) was performed after an intravenous bolus injection of Gd-DOTA (0.3 mmol kg(-1)). Temporal resolution was 0.6 s for hip and spine, and 0.3 s for knee. The total scan duration was 8 min for hip and spine, and 4.5 min for knee. The regions of interest for enhancement measurement included femoral head, proximal femoral diaphysis, distal femoral diaphysis and epiphysis, proximal tibial epiphysis and diaphysis, and lumbar vertebrae L1-5. RESULTS: Femoral head showed no enhancement signal decay during the DCE MRI period, while all other bony compartments showed a contrast washin phase followed by a contrast washout phase. In the knee joint, the contrast washout of the proximal tibia diaphysis was slower that of other bony compartments of the knee. CONCLUSION: Based on the evidence of delayed contrast washout, this study showed that blood perfusion in the femoral head could be compromised in normal rats.

Expression of glucose transporter-1, hypoxia-inducible factor-1α, phosphatidylinositol 3-kinase and protein kinase B (Akt) in relation to [(18)F]fluorodeoxyglucose uptake in nasopharyngeal diffuse large B-cell lymphoma: a case report and literature review.

This report presents a case of nasopharyngeal diffuse large B-cell lymphoma and a literature review concerning the use of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). A 37-year old man was admitted to hospital complaining of nasal secretions with minor epistaxis and a 20-year history of snoring. Nasal endoscopy found diffuse swelling in the nasopharynx and a biopsy was performed. Prior to chemotherapy, FDG-PET/CT showed soft tissue diffuse thickening and FDG accumulation in the nasopharynx and bilateral cervical lymph nodes; FDG did not accumulate elsewhere. After four cycles of chemotherapy (rituximab, cyclo phosphamide, doxorubicin, vincristine) and prednisone treatment, FDG-PET/CT showed that FDG still accumulated in the nasopharynx and bilateral cervical lymph nodes, therefore radiotherapy was initiated. At 1 year, FDG-PET/CT showed no FDG accumulation. Immunohistochemical analysis revealed that the tumour was positive for phosphorylated protein kinase B (Akt), suggesting that FDG uptake may be associated with factors activated by the phosphatidylinositol 3-kinase/Akt signalling pathway.

Anaplastic lymphoma kinase expression and prognosis in inflammatory myofibroblastic tumours of the maxillary sinus.

Inflammatory myofibroblastic tumours (IMT) of the nasal cavity and nasal sinus are rare and, although over 50 cases have been reported in the English-language literature, their precise aetiology and biological behaviour have not been elucidated. Recent studies suggest that anaplastic lymphoma kinase (ALK)-positive tumours have a very low risk of metastasis, but ALK reactivity does not appear to correlate with recurrence. Between March 2002 and December 2008, we encountered three cases of maxillary sinus IMT and investigated them to determine the clinicopathological course, prognosis and immunohistochemical expression of ALK. Two of the patients died < 13 months after the initial diagnosis and the third had multiple recurrences. All three cases were immunohisto chemically negative for ALK expression. IMT of the sino-nasal tract is rare and may undergo malignant transformation in a minority of cases. The three cases manifested progressive extension with bone destruction and multiple recurrences, and two cases had a fatal outcome and one case had high recurrence.

Kinetics of the thermal inactivation of alkaline phosphatase from green crab (Scylla serrata).

The kinetics of thermal inactivation of alkaline phosphatase from green crab (Scylla Serrata) has been studied using the kinetic method relating to the substrate reaction during irreversible inhibition of enzyme activity previously described by Tsou. The results show that the thermal inactivation of the enzyme is an irreversible reaction. Comparison of the microscopic rate constants for thermal inactivation of free enzyme and the enzyme-substrate complex shows that the presence of substrate has a certain protective effect against thermal inactivation.

Alkaline unfolding and salt-induced folding of yeast alcohol dehydrogenase under high pH conditions.

The conformational changes of yeast alcohol dehydrogenase during unfolding at alkaline pH have been followed by fluorescence emission and circular dichroism spectra. A result of comparison of inactivation and conformational changes shows that much lower values of alkaline pH are required to bring about inactivation than significant conformational change of the enzyme molecule. At pH 9.5, although the enzyme has been completely inactivated, no marked conformational changes can be observed. Even at pH 12, the apparently fully unfolded enzyme retains some ordered secondary structure. After removal of Zn2+ from the enzyme molecule, the conformational stability decreased. At pH 12 by adding the salt, the relatively unfolded state of denatured enzyme changes into a compact conformational state by hydrophobic collapsing. Folded states induced by salt bound ANS strongly, indicating the existence of increased hydrophobic surface. More extensive studies showed that although apo-YADH and holo-YADH exhibited similar behavior, the folding cooperative ability of apo-enzyme was lower than that of holo-enzyme. The above results suggest that the zinc ion plays an important role in helping the folding of YADH and in stabilizing its native conformation.

Kinetics of inhibition of alkaline phosphatase from green crab (Scylla serrata) by N-bromosuccinimide.

The inactivation of alkaline phosphatase from green crab (Scylla serrata) by N-bromosuccinimide has been studied using the kinetic method of the substrate reaction during modification of enzyme activity previously described by Tsou [(1988), Adv. Enzymol. Related Areas Mol. Biol. 61, 381-436]. The results show that inactivation of the enzyme is a slow, reversible reaction. The microscopic rate constants for the reaction of the inactivator with free enzyme and the enzyme-substrate complex were determined. Comparison of these rate constants indicates that the presence of substrate offers marked protection of this enzyme against inactivation by N-bromosuccinimide. The above results suggest that the tryptophan residue is essential for activity and is situated at the active site of the enzyme.

Comparison of inactivation and unfolding of green crab (Scylla serrata) alkaline phosphatase during denaturation by guanidinium chloride.

Green crab (Scylla serrata) alkaline phosphatase (EC 3.1.3.1) is a metalloenzyme, each active site in which contains a tight cluster of two zinc ions and one magnesium ion. Unfolding and inactivation of the enzyme during denaturation in guanidinium chloride (GuHCl) solutions of different concentrations have been compared. The kinetic theory of the substrate reaction during irreversible inhibition of enzyme activity previously described by Tsou [(1988), Adv. Enzymol. Related Areas Mol. Biol. 61, 381-436] has been applied to a study on the kinetics of the course of inactivation of the enzyme during denaturation by GuHCl. The rate constants of unfolding and inactivation have been determined. The results show that inactivation occurs before noticeable conformational change can be detected. It is suggested that the active site of green crab alkaline phosphatase containing multiple metal ions is also situated in a limited region of the enzyme molecule that is more fragile to denaturants than the protein as a whole.

Acid-induced folding of yeast alcohol dehydrogenase under low pH conditions.

Under conditions of low pH, the conformational states of holo-YADH and apo-YADH were examined by protein intrinsic fluorescence, ANS fluorescence, and far-UV CD measurements. The results obtained show that a low ionic strength, with the addition of HCl, the holo- and apo- YADH denatured gradually to reach the ultimate unfolded conformation in the vicinity of pH 2.0 and 2.5, respectively. With the decrease of pH from 7.0 to 2.0, the fluorescence emission decreased markedly, with its emission maximum red-shifting from 335 to 355 nm, indicating complete exposure of the buried tryptophan residues to the solvent. The far-UV CD spectra show the loss of the arrayed secondary structure, though the acid-denatured enzyme still maintained a partially arrayed secondary structure. A further decrease in pH by increasing the concentration of HClO4 induced a cooperative folding of the denatured enzyme to a compact conformation with the properties of a molten globule, described previously by Goto et al. [Proc. Natl. Acad. Sci. USA 87, 573-577 (1990)]. More extensive studies showed that although apo-YADH and holo-YADH exhibited similar behavior, the folding cooperative ability of apo-YADH was lower than that of the holo-enzyme. From the above results, it is suggested that the zinc ion plays an important role in the proper folding of YADH and in stabilizing its native conformation.

Kinetics of irreversible inhibition of yeast alcohol dehydrogenase during modification by o-phthaldehyde.

The kinetic theory of the substrate reaction during irreversible inhibition of enzyme activity described previously has been applied to a study on the kinetics of the course of inactivation of yeast alcohol dehydrogenase (YADH) by o-phthaldehyde (OPTA). The microscopic constants for the reaction of the inactivators with the free enzyme and with the enzyme-substrate complexes were determined. The inactivation is a monophasic pseudo-first-order reaction with OPTA. The apparent rate constant A is independent of the OPTA concentration, indicating that the inactivation is a noncomplexing inhibition. The marked protective effect of substrates on the inactivation of YADH by OPTA has been observed. This result suggests that the modification of the enzyme by OPTA may occur at the active site.