Prognostic factors of primary resected retroperitoneal soft tissue sarcoma: Analysis from a single asian tertiary center and external validation of gronchi's nomogram.

BACKGROUND: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. METHODS: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July 30th, 2011. The prognostic influence of clinicopathological characteristics as well as treatments on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were examined by univariate and multivariate analyses. A histology-specific nomogram developed by Gronchi et al was used for validation. RESULTS: Liposarcoma, leiomyosarcoma, and malignant peripheral sheath tumor (MPNST) were the most common histologies (70%). Multivariate analysis revealed FNCLCC tumor grade was the most significant prognostic factor for OS (P = 0.001) and DMFS (P < 0.001) and complete resection was the only significant prognostic factor for LRFS (P = 0.043). Incomplete resection of grade 3 tumor was significantly associated with a worse OS. Despite some differences in characteristics between our patients and Gronchi's cohort, external validation of Gronchi's nomogram demonstrated excellent concordance in predicting survival. CONCLUSIONS: Our study demonstrated tumor grade and surgical margins had significant prognostic influence and the Gronchi's nomogram has an excellent applicability in predicting survival of STS patients. J. Surg. Oncol. 2016;113:355-360. © 2016 Wiley Periodicals, Inc.

No increase of JAK2 46/1 haplotype frequency in essential thrombocythemia with CALR mutations: Functional effect of the haplotype limited to allele with JAK2V617F mutation but not CALR mutation.

The true frequency of the JAK2 46/1 haplotype in patients of myeloproliferative neoplasms (MPN) with CALR mutations was unknown. Totally 187 MPN cases with diagnosis of polycythemia vera (PV) and essential thrombocythemia (ET) were recruited. The frequency of 46/1 haplotype was significantly higher in JAK2V617F-positive PV (51%, p < 0.001) and ET (41%, p = 0.005) compared to normal controls. The exact location of JAK2V617F mutation was located at the cis-46/1 haplotype in 86.4% (32/37) PV patients and 87.5% (28/32) ET patients, respectively. Among the 51 patients of ET without JAK2V617F mutation, 38 (75%) patients harbored CALR mutations and 3 patients had MPL mutation. The frequency of 46/1 haplotype in the 38 ET patients with CALR mutations was 27%, which is not significantly different from that of normal control (p value = 0.879). Compared to non-46/1 haplotype, the presence of 46/1 haplotype had a trend to have higher white blood cell count in JAK2V617F-mutated PV and ET patients but not in CALR-mutated ET. We conclude that the 46/1 haplotype could have functioning effect but only in the context of JAK2V617F mutation.

Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia.

Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CALR mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 10(9)/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.

Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage.

BACKGROUND: Long-term outcomes are favorable for patients with polycythemia vera (PV) and for patients with essential thrombocythemia (ET). However, hemorrhage is a significant cause of morbidity and mortality in those patients. METHODS: We retrospectively recruited 247 patients who had received a diagnosis of PV (n = 101) or ET (n = 146) during the period 2001-2010. RESULTS: After a median follow-up period of 36.2 months, the cumulative incidence of hemorrhage was 39.6% in patients with PV (6.2% per person-year) and 29.7% in patients with ET (5.9% person-years). Episodes of major bleeding occurred in 9.9% of patients with PV and in 14.4% of patients with ET. Overall survival was significantly shorter among patients with hemorrhage than among those without said complication (P < 0.001 for overall patients; P = 0.002 for patients with PV; P = 0.026 for patients with ET). In the univariate analysis, age ≥ 60 yr (OR: 4.77, P = 0.046) and WBC ≥ 16 × 10(9) /L (OR: 4.15, P = 0.010) were predictors of hemorrhage in patients with PV, and age ≥ 60 yr (OR: 3.25, P = 0.040), WBC ≥ 16 × 10(9) /L (OR: 2.89, P = 0.024), albumin <4.0 g/dL (OR: 4.10, P = 0.002), and splenomegaly (OR: 5.19, P = 0.002) were predictors of hemorrhage in patients with ET. Multivariate analysis showed that WBC ≥ 16 × 10(9) /L was the only significant risk factor for hemorrhage in patients with PV (OR: 3.51, P = 0.026) and that splenomegaly was the only risk factor for hemorrhage in patients with ET (OR: 3.00, P = 0.048). CONCLUSION: Leukocytosis in PV and splenomegaly in ET are independent risk factors for hemorrhage.

Effects of anthracycline chemotherapy and Kuan-Sin-Yin on the spectral indices of arterial pulse waveforms in breast cancer patients.

The vascular structure and function are potentially useful biomarkers for tumor detection. Treatment with chemotherapeutic agents may impair vascular function and increase the risk of cardiovascular disease. This study aimed to use noninvasive pulse waveform measurements to identify differences in the frequency-domain indices of the pulse waveform in breast-cancer patients following anthracycline chemotherapy between with (Group KSY) and without (Group NKSY) receiving Kuan-Sin-Yin (KSY) treatment.Radial blood pressure waveform (BPW) signals were measured noninvasively for 3 minutes in 31 patients, and the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires were administered. The following pulse indices were calculated for 10 harmonics: the amplitude proportion and its coefficient of variation, and the phase angle and its standard deviation.The changes in spectral BPW indices were more prominent in Group NKSY than in Group KSY, especially for the decreases in BPW variability indices. Scores on the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires suggested that the quality of life following chemotherapy was better in Group KSY.The identified decreases in pulse variability indices could be related to the greater impairment of regulatory activities in Group NKSY. The present findings may be meaningful in developing techniques with advantages such as being noninvasive and time-saving to evaluate the blood supply and physiological conditions following chemotherapy or other treatment strategies in cancer patients.

Gonadotropin-releasing hormone agonist treatment and ischemic heart disease among female patients with breast cancer: A cohort study.

BACKGROUND: The risk of ischemic heart disease (IHD) due to the impact of gonadotropin-releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy. METHODS: Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new-onset IHD diagnosis, death, or December 31, 2018. A Kaplan-Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD. RESULTS: A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan-Meier survival curves showed a significant difference between patients with and without GnRH therapy (log-rank p < 0.0001). Patients who received GnRH therapy had a significantly decreased risk of developing IHD than those without GnRH therapy (HR = 0.18; 95% CI = 0.14-0.23). After adjusting for age, treatment, and comorbidity, patients who received GnRH therapy still had a significantly lower risk of developing IHD (AHR = 0.5, 95% CI = 0.39-0.64). CONCLUSION: The study showed that the use of GnRH agonists for breast cancer treatment was significantly associated with a reduced risk of IHD. Further research is required to investigate the possible protective effect of GnRH on IHD.

Pre-existing diabetes mellitus in patients with multiple myeloma.

OBJECTIVES: Type 2 diabetes mellitus is present in approximately 10% of patients at diagnosis of multiple myeloma (MM) and is associated with increased risks of adverse events caused by novel antimyeloma agents. However, the impact of type 2 diabetes on the survival of patients with MM has not been studied. METHODS: We enrolled newly diagnosed patients with MM in Taipei Veterans General Hospital between 1999 and 2007 and identified those with pre-existing diabetes. The impact of pre-existing diabetes on patients with MM was evaluated by comparing clinical features, treatments and adverse reactions related to glycaemic control and overall survival (OS) of patients with and without pre-existing diabetes. RESULTS: Of 310 patients with MM, 73% were men and 40 (12.9%) had pre-existing diabetes. Compared with their non-diabetic counterparts, MM patients with pre-existing diabetes had a significantly higher proportion of renal impairment [(RI), serum creatinine ≥ 2.0 mg/dL] and International Staging System stage III at diagnosis, and a significantly lower proportion of bisphosphonate use and a lower rate of RI reversal (P = 0.087). During the course of the disease, hyperglycaemia and hypoglycaemia of any grade were noted in 23 (67.6%) and 6 (17.6%) of these patients, respectively. Antidiabetic therapy was changed in 10 (29.4%) of 34 evaluable patients. MM patients with pre-existing diabetes had a significantly higher all-cause mortality risk (hazard ratio, 1.509; 95% confidence interval, 1.023-2.225, P = 0.037) compared with their non-diabetic counterparts. CONCLUSIONS: Our study demonstrated the impact of pre-existing diabetes on clinical features and OS in patients with MM.

Follow-up after primary treatment of soft tissue sarcoma of extremities: impact of frequency of follow-up imaging on disease-specific survival.

BACKGROUND AND OBJECTIVES: We explored the impact of frequency of surveillance imaging on disease-specific survival (DSS) in patients with extremity soft tissue sarcoma (STS). METHODS: Locoregional imaging (LRI) and chest imaging (CI) were used to detect local recurrence (LR) and distant metastasis (DM), respectively. Relapsing patients were retrospectively assigned to more frequent surveillance (MFS) or less frequent surveillance (LFS) groups, according to the median interval for each follow-up modality. Outcome measures included overall DSS (O-DSS), post-LR DSS, and post-DM DSS. RESULTS: We assigned 165 patients to three distinct risk groups according to tumor size (≤5 vs. >5 cm), depth (superficial- vs. deep-seated), grade (I vs. II or III), and surgical margin (≥10 vs. <10 mm). Data for 80 patients who relapsed were analyzed. Among 50 high-risk (with all four risk factors) relapsing patients, those in the MFS group for either LRI or CI had better O-DSS (LRI, median 44.07 vs. 27.43 months, P = 0.008; CI, median 43.60 vs. 36.93 months, P = 0.036), post-LR DSS (median 27.20 vs. 10.63 months, P = 0.028) and post-DM DSS (median 13.20 vs. 6.24 months, P = 0.031). CONCLUSION: More frequent follow-up were associated with improved survival in high-risk relapsing patients with extremity STS by providing greater opportunities for adequate reoperation.

Hospice Care Services Associated With a Lower Utilization of Life-Sustaining Treatments During End-Of-Life Care Among People Living With HIV/AIDS: A Population-Based Cohort Study.

Background: Hospice care involves improving quality of end-of-life (EOL) care and respecting patients' preferences regarding EOL treatment. However, the impact of hospice care services on the utilization of life-sustaining treatments during EOL care in patients with life-limiting diseases has not been extensively studied. Objectives: This nationwide cohort study aimed to determine the impact of hospice care services on the utilization of life-sustaining treatments during the last 3 months of life among people living with HIV/AIDS (PLWHA) in Taiwan. Methods: From 2000 to 2018, we identified adult PLWHA from Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined as positive HIV-1 Western blot. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, and defibrillation. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. Results: Of 5691 PLWHA, 2595 (45.9%) subjects utilized life-sustaining treatments during the last 3 months of life. After adjusting for other covariates, PLWHA with hospice care services were less likely to receive life-sustaining treatments during the last 3 months of life than those without the services (adjusted odds ratio [AOR] = .50, 95% confidence interval [CI]: .37-.66). Considering the type of life-sustaining treatments, hospice care services were associated with lower likelihood of receiving cardiopulmonary resuscitation (AOR = .22, 95% CI: .13-.39), endotracheal intubation (AOR = .48, 95% CI: .35-.65), and mechanical ventilation support (AOR = .56, 95% CI: .42-.75). Conclusion: Hospice care services were associated with a lower utilization of life-sustaining treatments during the last 3 months of life among PLWHA.

Brain, the last fortress of sarcoma: similar dismal outcome but discrepancy of timing of brain metastasis in bone and soft tissue sarcoma.

BACKGROUND AND OBJECTIVE: Brain metastasis is a rare but dismal event in sarcomas. However, the pattern of occurrence and the prognostic factors associated with post-brain metastasis survival (PBMS) are not yet well-characterized. METHODS: Sarcoma patients treated at one institute within 10-year period were retrospectively reviewed and those with brain metastasis were identified. The incidence of brain metastasis was demonstrated by case per person-years and cumulative incidence curves. Univariate factors associated with PBMS were analyzed. RESULTS: Among 611 sarcoma patients, 20 (3.3%) developed brain metastasis. Alveolar soft part sarcoma (ASPS) and osteosarcoma were the most common subtypes. Overall, the cumulative incidence was 3.9% at 5 years and 8.4% at 10 years. However, the incidence in STS patients continued to rise up to 10 years after primary diagnosis, whereas it reached a plateau in bone sarcoma patients at 3 years. Median PBMS was 1.67 months. Univariate factors associated with better PBMS included ASPS histology, initial surgical treatment, and brain irradiation for non-surgically treated patients. CONCLUSION: Our study revealed a discrepancy in the timing of occurrence of brain metastasis between STS and bone sarcoma. However, patients with brain metastasis had a poor prognosis, implicating the brain as the last fortress of sarcoma.

Association of Hospice Care Services With the Utilization of Life-Sustaining Treatments During End-of-Life Care Among Patients With Cancer: A Nationwide 11-Year Cohort Study.

CONTEXT: The impact of hospice care services on the utilization of life-sustaining treatments during end-of-life care in terminally ill patients has not been extensively studied. OBJECTIVES: To determine the impact of hospice care services on the utilization of life-sustaining treatments during the last three months of life among patients with cancer. METHODS: This nationwide population-based cohort study identified adults with cancer diagnosis from the Taiwan Registry for Catastrophic Illness, 2006-2016. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, nasogastric tube feeding, and total parenteral nutrition. Hospice care services consisted of hospice inpatient care, hospice-shared care, and hospice home care. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. RESULTS: Of 516,409 patients with cancer, 310,722 (60.2%) patients used life-sustaining treatments during the last three months of life. After adjusting for covariates, patients with hospice care services were less likely to receive life-sustaining treatments during the last three months of life than those without the services (adjusted odds ratio [AOR]: 0.70; 95% CI: 0.69-0.71). While type of life-sustaining treatments were considered, hospice care services were associated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR: 0.125; 95% CI: 0.118-0.131), endotracheal intubation (AOR: 0.204; 95% CI: 0.199-0.210), mechanical ventilation support (AOR: 0.265; 95% CI: 0.260-0.270), nasogastric tube feeding (AOR: 0.736; 95% CI: 0.727-0.744), and total parenteral nutrition (AOR: 0.86; 95% CI: 0.84-0.88). CONCLUSION: Hospice care services were associated with a lower likelihood of receiving life-sustaining treatments during the last three months of life in patients with cancer.

Low Socioeconomic Status Associated With Lower Utilization of Hospice Care Services During End-of-Life Treatment in Patients With Cancer: A Population-Based Cohort Study.

CONTEXT: Socioeconomic status (SES) is an important determinant of disparities in health services and may affect the utilization of hospice care services during end-of-life (EOL) treatment in patients with cancer. However, previous studies evaluating the association between SES and utilization of hospice care services among patients with cancer revealed inconsistent findings. OBJECTIVES: This study aimed to determine the association between SES and utilization of hospice care services during the last year of life in patients with cancer. METHODS: From January 1, 2006 to December 31, 2016, we identified adults with cancer diagnoses from the Registry for Catastrophic Illness in Taiwan. The cancer diagnoses in study subjects were proved by the pathohistological reports. The utilization of hospice care services during the last year of life in patients with cancer included hospice inpatient care, hospice-shared care, and hospice home care. RESULTS: In the follow-up period, 28.6% of 516,409 patients with cancer used hospice care services during the last year of life. After adjusting for other covariates, low SES significantly reduced the utilization of hospice care services by 18% during the last year of life in patients with cancer. Moreover, a positive trend between decreasing levels of SES and lower utilization of hospice care during EOL treatment was noted (P < 0.001). CONCLUSION: Low SES was associated with lower utilization of hospice care services during EOL care in patients with cancer. Our data support the need to target low SES patients with cancer in efforts to optimally increase hospice care services during EOL care.

Comparison of complexity and spectral indices of skin-surface laser-doppler signals in patients with breast cancer receiving chemotherapy and Kuan-Sin-Yin.

This study tested the hypothesis that measuring and analyzing skin-surface blood flow dynamics can be used to noninvasively discriminate the different microcirculatory and physiological function states of breast-cancer patients with chemotherapy between receiving and not receiving Kuan-Sin-Yin (KSY) treatment. The 17 included patients were assigned randomly to 2 comparison groups: Group K (n = 10) received KSY treatment, while Group NK (n = 7) did not receive KSY treatment. Beat-to-beat, spectral, and approximate-entropy (ApEn) analyses were applied to the 20-minute laser-Doppler sequences. The self-reported quality of life and cancer-related symptoms of patients were also investigated. In posttests, Group NK had a significantly larger ApEn ratio than that in Group K, significantly smaller values of laser-Doppler-flowmetry variability indices, and a slightly higher relative energy contribution of the neural-related frequency band compared to those in the pretests. Almost all cancer-related symptoms showed improvements in Group K compared to in Group NK. The present findings indicated that the present analysis can be used to detect the significantly different responses in the laser-Doppler indices between taking and not taking KSY. The KSY effect was also noted to be accompanied with improvement of EORTC QLQ-C30 scores. These could lead to a rapid, inexpensive, and objective technique for enhancing clinical applications in quality-of-life monitoring of breast cancer therapy.

Aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer: A population-based analysis.

As reported by the Taiwan Cancer Registry in 2013 squamous cell carcinoma of head and neck cancer (HNSCC) was the sixth most frequently diagnosed cancer and the 5th most common cause of cancer related death and its incidence and mortality rate is still rising. The co-occurrence of HNSCC and secondary primary cancer (SPC) and the chemopreventive effect of aspirin on certain malignancies had been reported. Therefore we conducted this national study to investigate the use of aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer in Taiwan. We searched the Registry for Catastrophic Illness in the National Health Insurance Research Database (NHIRD) for 18,234 patients (3,576 aspirin users and 14,667 non-aspirin users) diagnosed with HNSCC during 2000-2005. The SPC incidence density during follow-up in 2000-2011 was compared between the groups. For HNSCC patients, aspirin use after diagnosis was significantly associated with SPC risk reduction by 25% (adjusted HR, 0.75; 95% CI, 0.63-0.89; p = 0.001) after multivariate analysis. In the subgroup analysis, we found that esophageal cancer and stomach cancer incidence were significantly reduced after aspirin use (adjusted HR, 0.60; 95% CI, 0.41-0.90; p = 0.01 for esophageal cancer; adjusted HR, 0.27; 95% CI, 0.08-0.87; p = 0.03 for stomach cancer). Aspirin use for 1-3 years was associated with SPC risk reduction by 35% (adjusted HR, 0.65; 95% CI, 0.49-0.87; p = 0.003). SPC risk reduction extended continuously for more than 3 years of follow up (adjusted HR, 0.72; 95% CI, 0.53-0.98; p = 0.030). Our data shows aspirin use was associated with reduced SPC incidence for HNSCC patients, attributed mainly to reduced risk of esophageal and stomach cancer.

Effect of Tai Chi Synergy T1 Exercise on Autonomic Function, Metabolism, and Physical Fitness of Healthy Individuals.

OBJECTIVES: Tai Chi synergy T1 exercise is an aerobic exercise derived mainly from Tai Chi exercise. It is also derived from the Eight Trigrams Palms, form and will boxing, mantis boxing, Qigong, and Yoga, with a total of 16 sessions in 63 minutes. In this study, we investigated its effects on autonomic modulation, metabolism, immunity, and physical function in healthy practitioners. METHOD: We recruited a total of 26 volunteers and 23 control participants. Heart rate variability (HRV), blood pressure, and body mass index (BMI) were recorded before and after practicing Tai Chi synergy T1 exercise and regular walking for 10 weeks, respectively. Serum glucose, cholesterol, and peripheral blood including B and T cell counts were also measured. They underwent one-minute bent-knee sit-ups, sit and reach test, and three-minute gradual step test. RESULTS: Tai Chi synergy T1 exercise enhanced parasympathetic modulation and attenuated sympathetic nerve control with increased very low frequency (VLF) and high frequency (HF) but decreased low frequency (LF) compared to the control group. Metabolic profiles including serum glucose, cholesterol, and BMI significantly improved after exercise. The exercise enhanced innate and adaptive immunity by increasing the counts of CD3+ T cells, CD19+ B cells, and CD16+CD56+ NK cells but decreasing the CD3+ cytotoxic T cell count. All monitored parameters including physical fitness and physical strength improved after the exercise. CONCLUSION: Tai Chi synergy T1 exercise improves autonomic modulation, body metabolism, physical fitness, and physical strength after 10 weeks of practice.

Cardiac Autonomic Function in Patients With Ankylosing Spondylitis: A Case-Control Study.

Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS.The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G).Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0-0.5 Hz) and high-frequency power (HF, 0.15-0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04-0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters.AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients.

Cytotoxic mechanism of PLK1 inhibitor GSK461364 against osteosarcoma: Mitotic arrest, apoptosis, cellular senescence, and synergistic effect with paclitaxel.

Polo-like kinase 1 (PLK1), a serine/threonine kinase and an oncogene, is crucial in regulating cell cycle progression. PLK1 also has been demonstrated as a potential target of osteosarcoma (OS) by using short hairpin RNA libraries in lentiviral vectors for screening of protein kinase. In preclinical studies, GSK461364, a potent and selective ATP-competitive PLK1 inhibitor, showed antiproliferative activity against multiple tumor cell lines. In the present study, we evaluated the expression level of PLK1 in OS and explored the cytotoxic mechanism of GSK461364 against OS. PLK1 was significantly overexpressed in OS compared with normal osteoblasts and other types of sarcoma. GSK461364 inhibited PLK1 and caused mitotic arrest by inducing G2/M arrest in OS cells. Moreover, GSK461364 exerted a cytotoxic effect by inducing apoptosis in OS, and induced cellular senescence in OS cell lines, as indicated by an increased senescence-associated ß-galactosidase activity and enhanced DcR2 and interleukin-1α expression. In addition, we demonstrated a synergistic cytotoxic effect of GSK461364 and paclitaxel, possibly resulting from combined mitotic arrest. In conclusion, the present study revealed that PLK1 was overexpressed in OS and that GSK461364 exerted its cytotoxic effect on OS by inducing mitotic arrest and subsequent apoptosis and induced cellular senescence; therefore, senescence-associated markers can be used as treatment biomarkers, and a combination of GSK461364 and paclitaxel can potentially treat OS.

Epithelial-mesenchymal transition-related factors in solid tumor and hematological malignancy.

The epithelial-mesenchymal transition (EMT) process plays pivotal roles in regulatory mechanisms of embryogenesis and wound healing physiologically, and organ fibrosis, cancer progression, and metastasis pathologically. EMT is classified as primary, secondary, and tertiary during embryonic development. EMT contributes to repair of tissue injury and fibrogenesis by re-epithelialization and regeneration of fibroblasts, respectively. The hallmarks of EMT include loss of contact inhibition, remodeling of extracellular matrix, and reorganization of cytoskeleton, along with expression of mesenchymal markers and reduction of epithelial markers. Cancer cells acquire stemness, migration and invasive capability, evade apoptosis, and initiate metastasis to distant organs. Several EMT regulators including Snail, Zeb1, Zeb2, and Twist in solid tumor and Sox4, distal-less homeobox gene 4 (DLX4), Prdm14, Bmi1, and the forkhead box family in hematological malignancy are reviewed with regard to their signaling pathways, regulatory mechanisms, and clinical interactions.