This study investigates whether the appendicular skeletal muscle index (ASMI) was an independent prognostic predictor for patients with locally advanced head and neck cancer (LAHNC) receiving ...concurrent chemoradiotherapy (CCRT) and whether there were any differences in lean mass loss in different body regions during CCRT.
In this prospective study, we analyzed the clinicopathological variables and the total body composition data before and after treatment. The factors associated with the 2-year recurrence-free survival rate (RFSR) were analyzed via logistic regression analysis.
A total of 98 patients were eligible for analysis. The body weight, body mass index, and all parameters of body composition significantly decreased after CCRT. The pretreatment ASMI was the only independent prognostic factor for predicting the 2-year RFSR (hazard ratio, 0.235; 95% confidence interval, 0.062-0.885;
= 0.030). There was at least 5% reduction in total lean and fat mass (
< 0.001); however, the highest lean mass loss was observed in the arms (9.5%), followed by the legs (7.2%), hips (7.1%), waist (4.7%), and trunk (3.6%).
The pretreatment ASMI was the only independent prognostic predictor for the 2-year RFSR of LAHNC patients undergoing CCRT. Asynchronous loss of lean mass may be observed in different body parts after CCRT.
Insulin receptor substrate 2 (IRS2) is a candidate driver oncogene frequently amplified in cancer and is positively associated with IRS2 expression. The overexpression of IRS2 has been suggested to ...promote tumor metastasis. However, its function in intrahepatic cholangiocarcinoma (iCCA) has not been investigated extensively. The present study examined 86 cases of iCCA to analyze IRS2 expression and its correlation with clinicopathological characteristics using immunohistochemical assays. Three stable cell lines overexpressing IRS2 were established. The mobility potential of cells was compared in the basal condition and following manipulation using cell migration and invasion assays. Epithelial-mesenchymal transition (EMT)-associated proteins were assessed by western blotting. IRS2 was overexpressed in 29 iCCA cases (33.7%) and was significantly more frequent in cases with large tumor size (P=0.033), classified as an advanced stage by the American Joint Committee on Cancer (P=0.046). In comparison with the control cells, the three IRS2-overexpressing iCCA cell lines exhibited a statistically significant increase in mobility potential. Expression analysis of EMT markers demonstrated decreased epithelial marker levels and increased mesenchymal marker levels in IRS2-overexpressing cells compared with their corresponding control cells. The results of the present study indicate that IRS2 overexpression is characterized by a large tumor size and advanced tumor stage in iCCA, and that it may increase tumor mobility potential by regulating EMT pathways. Therefore, it is a valuable predictive indicator of metastasis and may provide a novel direction for targeted therapy in iCCA.
The average prevalence of hepatitis C virus (HCV) infection in renal transplant recipients is 10%. Studies of these patients with HCV infection usually focuses on long-term graft survival and patient ...survival. Studies of the correlation between HCV infection and bone mineral density (BMD) in renal transplant patients are limited. The aim of this study was to investigate whether HCV infection is a risk factor for BMD change during a short follow-up period.
Seventy-six renal transplant recipients underwent 2 separate dual-energy X-ray absorptiometry (DXA) scans during a mean period of 14 months. Fifteen patients were HCV infection. First bone mineral density (BMD) at the lumbar spine, hip, and femoral neck was determined using dual-energy X-ray absorptiometry (DXA) between September 2008 and March 2009. After that, 34 patients took alendronate sodium 70 mg per week. Subgroups risk factors analysis was also performed into with or without alendronate. Immunosuppressive agents, bisphosphonates, patient characteristics, and biochemical factors were analyzed to identify associations with BMD.
After 14 months, in 76 patients, BMD of the lumbar spine had significantly increased (from 0.9 g/cm² to 0.92 g/cm², p<0.001), whereas BMD of the hip and femoral neck had not. Multiple linear regression analysis showed that HCV infection was negatively associated with BMD change in the lumbar spine ( β: -0.247, 95% CI, -0.035 to -0.002; p = 0.028). Moreover, in subgroup analysis, among 42 patients without alendronate, multiple linear regression analysis showed HCV infection was a risk factor for adverse BMD change of the lumbar spine ( β: -0.371, 95% CI, -0.043 to -0.003; p = 0.023).
HCV infection in renal transplant recipients was a negative risk factor for BMD change in the lumbar spine. Moreover, alendronate may be able to reverse the negative effect of HCV infection on bone in renal transplant recipients.
Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized ...the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis. Further, tubulin was depolymerized by 21-900 in a manner similar to that of vincristine, leading to disruption of microtubule dynamics and increased levels of the mitotic marker MPM-2. Further, 21-900 increased the expression of cleavage form of poly (ADP-ribose) polymerase (PARP), caspase 3, 7 (cleavage form), and pro-apoptotic protein BAK and decreased the expression of pro-survival BCL-2-family proteins BCL-2, MCL-1, and BID pro-form, leading to the induction of apoptosis. The growth of tumours in nude mice formed by xenografts of HL-60 and MOLT-4 cells was significantly inhibited by 21-900 without causing the mice to lose body weight. These findings indicate that 21-900 may serve as a potent anti-leukaemia drug.
Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, and as such, it is an ...essential target in medicine and cosmetics. Known tyrosinase inhibitors possess adverse side effects, and there are no safety regulations; therefore, it is necessary to develop new inhibitors with fewer side effects and less toxicity. Peptides are exquisitely specific to their in vivo targets, with high potencies and relatively few off-target side effects. Thus, we systematically and comprehensively investigated the tyrosinase-inhibitory abilities of N- and C-terminal cysteine/tyrosine-containing tetrapeptides by constructing a phage-display random tetrapeptide library and conducting computational molecular docking studies on novel tyrosinase tetrapeptide inhibitors. We found that N-terminal cysteine-containing tetrapeptides exhibited the most potent tyrosinase-inhibitory abilities. The positional preference of cysteine residues at the N terminus in the tetrapeptides significantly contributed to their tyrosinase-inhibitory function. The sulfur atom in cysteine moieties of N- and C-terminal cysteine-containing tetrapeptides coordinated with copper ions, which then tightly blocked substrate-binding sites. N- and C-terminal tyrosine-containing tetrapeptides functioned as competitive inhibitors against mushroom tyrosinase by using the phenol ring of tyrosine to stack with the imidazole ring of His263, thus competing for the substrate-binding site. The N-terminal cysteine-containing tetrapeptide CRVI exhibited the strongest tyrosinase-inhibitory potency (with an IC50 of 2.7 ± 0.5 μM), which was superior to those of the known tyrosinase inhibitors (arbutin and kojic acid) and outperformed kojic acid-tripeptides, mimosine-FFY, and short-sequence oligopeptides at inhibiting mushroom tyrosinase.
The aim of this study is to solve an inverse heat conduction problem to estimate the unknown time-dependent laser irradiance and thermal damage in laser-irradiated biological tissue from the ...temperature measurements taken within the tissue. The dual-phase-lag model is considered in the formulation of heat conduction equation. The inverse algorithm used in the study is based on the conjugate gradient method and the discrepancy principle. The effect of measurement errors and measurement locations on the estimation accuracy is also investigated. Two different examples of laser irradiance are discussed. Results show that the unknown laser irradiance and thermal damage can be predicted precisely by using the present approach for the test cases considered in this study.
To assess surgical outcomes in synchronous multiple primary lung cancer (SMPLC) and correlations with clinicopathological features and prognostic/predictive factors.We retrospectively reviewed ...patients diagnosed with early-stage nonsmall cell lung cancer (NSCLC) between January 2006 and June 2012. In total, 564 patients with resectable NSCLC underwent a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 35 SMPLC patients. Surgical outcomes, prognosis, and tumor imaging features were evaluated (median follow-up = 44 months).In total, 35 eligible SMPLC patients (6.21%) were identified (11 men 31%, 24 women 69%, mean age = 65 years). The tumors were bilateral in 17 patients (49%) and in different lobes of the ipsilateral lung in 18 patients (51%). Most patients (26/35, 74%) had 2 primary tumors, and 26% (9/35) had more than 2 tumors (6 with 3 tumors; 3 with 4 tumors). The median size of the most advanced tumor was 3.0 cm (range 0.9-54). The median standard uptake value (SUV) of the largest tumor was 3.1 (range 1.0-13.3). The patients were treated as follows: 30 lobectomies, 2 sublobar resections, 2 sequential bilateral lobectomies, and 1 bi-lobectomy. Twenty-four patients (69%) received adjuvant therapy. The overall cumulative 5-year survival was 91.5% (median overall survival = 45.5 months). Patients with a reference tumor ≤ 3 cm and SUV ≤ 3.1 had an expected 5-year survival of 100%. Patients with a reference tumor > 3 cm and SUV > 3.1 had an expected 5-year survival rate of 53.3%.SMPLC patients can benefit from aggressive surgery. The size and SUVmax of the reference tumor may predict postoperative outcomes.
In this study, an inverse algorithm based on the conjugate gradient method and the discrepancy principle is applied to solve the inverse hyperbolic heat conduction problem in estimating the unknown ...space- and time-dependent base heat flux of a cylindrical pin fin from the knowledge of temperature measurements taken within the medium. The inverse solutions have been justified based on the numerical experiments in which three specific cases to determine the unknown base heat flux are examined. The temperature data obtained from the direct problem are used to simulate the temperature measurements. The influence of measurement errors upon the precision of the estimated results is also investigated. Results show that an excellent estimation on the space- and time-dependent base heat flux can be obtained for the test cases considered in this study.
Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by International Society for Holter and Noninvasive ...Electrocardiography (ISHNE) and Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society (HRS/EHRA/APHRS) were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before.
This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria.
A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased by 71%. However, all-cause mortality and cardiovascular mortality were not different between individuals with or without BrP, irrespective of the criteria used.
The two different criteria may impact the diagnostic yield of individuals with BrP, but do not affect the prognosis of the individuals with BrP. Key messages Comparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria. The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different.
In this study, an inverse algorithm based on the conjugate gradient method and the discrepancy principle is applied to solve the inverse heat conduction problem with a dual-phase-lag equation for ...estimating the unknown space- and time-dependent laser-induced heat generation in a gas-saturated porous medium exposed to short-pulse laser heating from the temperature measurements taken within the medium. Subsequently, the powder particle temperature distributions in the porous medium can be determined as well. The temperature data obtained from the direct problem are used to simulate the temperature measurements. The effect of measurement errors on the estimation accuracy is also investigated. The inverse solutions are justified based on the numerical experiments in which two different forms of heat generation are estimated. Results show that the unknown laser-induced heat generation can be predicted precisely by using the present approach for the test cases considered in this study.
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