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Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system’s reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient’s reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Objectives This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population.Methods Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE.Results In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p

Abstract Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p

PurposeThis research aimed to analyze electron stream effect (ESE) during magnetic resonance image guided radiotherapy (MRgRT) for breast cancer patients on a MR-Linac (0.35 Tesla, 6MV), with a focus on the prevention of redundant radiation exposure.Materials and methodsRANDO phantom was used with and without the breast attachment in order to represent the patients after breast conserving surgery (BCS) and those received modified radical mastectomy (MRM). The prescription dose is 40.05 Gy in fifteen fractions for whole breast irradiation (WBI) or 20 Gy single shot for partial breast irradiation (PBI). Thirteen different portals of intensity-modulated radiation therapy were created. And then we evaluated dose distribution in five areas (on the skin of the tip of the nose, the chin, the neck, the abdomen and the thyroid.) outside of the irradiated field with and without 0.35 Tesla. In addition, we added a piece of bolus with the thickness of 1cm on the skin in order to compare the ESE difference with and without a bolus. Lastly, we loaded two patients’ images for PBI comparison.ResultsWe found that 0.35 Tesla caused redundant doses to the skin of the chin and the neck as high as 9.79% and 5.59% of the prescription dose in the BCS RANDO model, respectively. For RANDO phantom without the breast accessory (simulating MRM), the maximal dose increase were 8.71% and 4.67% of the prescription dose to the skin of the chin and the neck, respectively. Furthermore, the bolus we added efficiently decrease the unnecessary dose caused by ESE up to 59.8%.ConclusionWe report the first physical investigation on successful avoidance of superfluous doses on a 0.35T MR-Linac for breast cancer patients. Future studies of MRgRT on the individual body shape and its association with ESE influence is warranted.

Abstract Background The optimal radiotherapy dose for locally advanced esophageal squamous cell carcinoma in endemic areas treated with neoadjuvant concurrent chemoradiotherapy is unclear. Methods Eligible patients diagnosed between 2010 and 2019 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders. The hazard ratio (HR) of death was compared between high dose (50–50.4 Gy) and low dose (40–41.4 Gy) radiotherapy. We also evaluated other outcomes and performed supplementary analyses via an alternative approach. Results Our study population consisted of 644 patients. The PS weight-adjusted HR of death was 0.92 (95% confidence interval: 0.7–1.19, p = 0.51). There were no statistically significant differences for other outcomes or supplementary analyses. Conclusions In this population-based study from an endemic area, we found no significant difference in overall survival between high vs. low radiotherapy doses.

Abstract Background Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE. Methods A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package. Results Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA. Conclusions We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.

Abstract Background The optimal radiotherapy dose for locally advanced cervical esophageal squamous cell carcinoma (C‐ESqCC) treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. Here, we aimed to compare the survival of those treated with high dose versus standard dose via a population based approach. Methods Eligible C‐ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between high (60–70 Gy) and standard dose (50–50.4 Gy). We also evaluated the outcome in supplementary analyses via alternative approaches. Results Our primary analysis consisted of 141 patients in whom covariates were well balanced after PS weighting. The HR of death when high dose was compared with standard dose was 0.65 (95% confidence interval [CI]: 0.4–1.03, p = 0.07). The HR of IECM was 0.74 (p = 0.45). The HR of OS remained similarly insignificant in supplementary analyses. Conclusions We observed a trend in favor of high radiotherapy dose versus standard dose for C‐ESqCC treated with dCCRT in this population‐based nonrandomized study. Further studies are needed to confirm the findings of the study.

Abstract Background The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. Methods Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. Results Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24–0.53, P

Cancer registries are critical databases for cancer research whose maintenance requires various types of domain knowledge with labor-intensive data curation. In order to facilitate the curation process with high quality in a timely manner, we developed a hybrid neural symbolic system for cancer registry coding. Unlike previous works which mainly worked on the dataset collected from one hospital or formulated the task as text classification problems, we collaborated with two medical centers in Taiwan to compile a cross-hospital corpus and applied neural networks to extract cancer registry variables described in unstructured pathology reports along with expert systems for generating registry coding. We conducted experiments to study the feasibility of the proposed hybrid for the task of cancer registry coding and compare its performance with state-of-the-art non-hybrid approaches. Furthermore, cross-hospital experiments were performed to study the advantages and limitations of transfer learning for processing reports from different sources. The experiment results demonstrated that the proposed hybrid neural symbolic system is a robust approach which works well across hospitals and outperformed classification-based baselines by F-scores of 0.13~0.27. Compared to the baseline models, the F-scores of the proposed approaches are apparently higher when fewer training instances were used. All methods benefited from the transferred parameters learned from the source dataset, but the results suggest that it is a better strategy to transfer the learned knowledge through the concept recognition task followed by the symbolic expert system to address the task of cancer registry coding.

Abstract Background This study investigated the impact of post-radiation sinusitis on the prognosis of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT). Methods Two hundred and thirty patients with non-metastatic NPC were analyzed in terms of freedom from local failure (FFLF), freedom from distant failure (FFDF), overall survival (OS), and disease-free survival (DFS). For each patient, the status of the sinus mucosa was flexibly assessed by documenting mucosal changes as indicated by differences between images obtained before radiotherapy and more than 6 months post-radiation. Results With a median follow-up of 39.7 months (8 to 81 months), 19 (8.26%) patients relapsed locally, 13 (5.65%) patients failed in the neck, and 26 (11.3%) patients developed distant metastases. The presence of sinusitis noted in images post-radiation was a significant predictor for DFS (p = 0.001), FFLF (p = 0.004), and FFDF (p = 0.015), in addition to having high negative predictive value for local relapse (97.5%). Conclusions This is the first study to investigate the prognostic value of post-radiation sinusitis in NPC patients treated with IMRT. Post-radiation sinusitis was found to be a significant predictor for DFS, FFLF, and FFDF, and was also found to have high negative predictive value for local recurrence (97.5%). It may thus be used as an additional tool for clinicians to determine the possibility of recurrence.

This paper examines the relationship between the escalation in housing prices and categories of Taiwan’s domestic consumption. While disposable income remains constant, a rapid escalation in housing prices should have a negative impact on unaffordability within society. However, under the hypothesis of the housing wealth effect, an increase in housing values should compensate the macro-economy by increasing consumption in the GDP calculation. Taiwanese data from 2007Q1 to 2018Q1 were adopted as the sample. From the vector error correction model results, it was found that over the course of the long-run equilibrium relationship, there was a statistically significant positive relationship that the society consumes more on durable goods of communication-related nature, as well as on non-durable goods such as personal clothing and accessories and leisure/cultural tourism. As for the short-run dynamic adjustment, there was a statistically significant positive relationship that the society consumes more in the durable goods component categories. It was identified that transportationrelated consumption accounted for the major part of the durable goods component. Therefore, with the rapid escalation in housing prices, it was observed that these consumption would compensate the consumption figures in the GDP calculation in Taiwan, thereby providing evidence that housing prices were related to macroeconomic performance.

Liver abscess caused by foreign-body penetration of the alimentary tract is rare. Preoperative diagnosis is difficult as patients are often unaware of the foreign-body ingestion and the unusual characteristic is often being paucisymptomatic until secondary complications occur. We report a patient with fishbone-related liver abscess. Preoperative demonstration of a hyperdense, linear lesion was performed by computed tomography. He was treated successfully after removal of the foreign body and drainage of the abscess.

Background: We aimed to determine whether higher neutrophil counts (NC) and neutrophil-to-lymphocyte ratio (NLR) were independently predictive of worse in-hospital outcome in patients after acute ischemic stroke (IS). Methods: A retrospective observational study with prospective manner of IS registration. Between April 2012 and August 2014, a total number of 1731 patients with post-IS were consecutively enrolled in the study. Blood samples were drawn upon admission. Primary endpoint was in-hospital mortality. Secondary endpoint was severe stroke (≥16 NIHSS). Results: The NC progressively increased from mild (NIHSS ≤ 5) to moderate (NIHSS ≥ 6 74% had a 2.54-fold increased risk of severe stroke (OR = 1.82–3.54) compared to patients with NC

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future.

Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.

This paper provides a comprehensive investigation on the causality relationship between fund performance and trading flows. We analyze if investors behave asymmetrically in fund purchasing and selling by seemingly unrelated regression which comprises several individual relationships that are linked by the fact that their disturbances or the error terms are correlated. The empirical result shows a significantly negative relationship between fund performance and purchase flows for domestic funds. The magnitude of domestic funds redemption negatively affects current return, but not for international funds. As previousfund return positively affects current net flows,the further lagged performances have no significant impact on the trading flows, revealing that fund investors are sensitive only to short-term past performance. Most importantly, while negative fund performance leads to the increases in redemption, positive performance contrarily leads to the decreases in purchase. The evidences strongly indicate an asymmetry behavior of fund investors in the return-purchase causality relations.

Concomitant ductal carcinoma in situ (DCIS) and ipslateral gynecomastia (GM) are very rarely reported in male

This study aims to examine whether funds with illiquid assets exhibit stronger sensitivity of redemption outflows to bad past performance than funds with liquid assets. An important aspect of our study is whether large outflows should damage future fund performance in illiquid funds more than in liquid funds. When redeemed in a large scale, the liquidity risk of open-end funds will increase, which in turn leads to a vicious circle between fund redemption and the net asset value decline. Accordingly, Stepwise Reality Check method is taken into account of the financial stability problem and to control for the data-snooping bias. Based on the sample of underperformed mutual funds in Taiwan, the empirical results show that (1) bad past performance in liquid funds is more sensitive on flow-performance relations; (2) The evidence in (1) exists only for institutional-oriented funds, but not for retail-oriented funds; and (3) Illiquid funds damage from a large number redemptions with significant return persistence. The above findings provide valuable references for fund managers to make the plan of their investments.

Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP) bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle-aged woman with a history of breast cancer with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) diagnosis simultaneously. Based on imaging of 18F-FDG PET/CT, diffusely incremental 18F-FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm-related endocrine factors.

Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients. Methods: A total of 78 patients with rectal cancer were enrolled. Patients were administered chemoradiotherapy, which comprised radiotherapy and chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Surgery was performed 10–12 weeks after radiotherapy completion. Tumor regression, adverse events, surgical complications, and short-term clinical outcomes were recorded. Results: Two patients were excluded because of incomplete radiotherapy treatment or refusal of surgery. Eventually, 76 patients underwent total mesorectal excision and no perioperative mortality was observed. Of these, 20 patients (25.6%) developed grade 3 or 4 toxicity during concurrent chemoradiotherapy. Among the 76 patients who underwent surgery, 24 (31.6%) patients achieved a pathologic complete response. The sphincter preservation rate was 96.1% (73/76) in all patients and 92.2% (39/42) in patients with tumors located less than 5 cm from the anal verge. The 2-year overall and disease-free survivals were 94% and 87.4%, respectively. Conclusion: The intensified multimodality therapy was well tolerated in our cohort and resulted in a considerably high pathologic complete response rate. Regardless of favorable short-term clinical outcomes, long-term oncologic outcomes will be closely monitored among the patients with a pathologic complete response.

To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast cancer patients with and without immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction.The study included 492 patients with stage II or III breast cancer who underwent modified radical mastectomy (MRM) and chemotherapy followed by PMRT between 1997 and 2011. Cox regression model and Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease-free survival rates in the 2 groups.Among 492 patients, 213 patients had immediate TRAM flap reconstruction. The mean follow-up was 7.2 years (range, 11-191 months). The 5-year and 10-year disease free survival rates were 81% and 76% for the TRAM flap group and 78% and 73% for the non-flap group. The 5-year and 10-year overall survival rates were 89% and 73% for the TRAM flap group and 83% and 74% for the non-flap group.There exists no statistically significant difference in the rates of local recurrence, distant metastasis, disease-free and overall survival when comparing immediate TRAM flap reconstruction with no reconstruction. Our results suggest that immediate TRAM flap reconstruction does not compromise long term clinical outcomes in breast cancer patients requiring PMRT.

The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an oncogene addiction phenomenon. In xenograft tumor-bearing mice, CYT-Rx20 significantly reduced tumor growth of the implanted esophageal cancer cells accompanied by decreased Ki-67, phospho-AKT, and phospho-STAT3 expression. In orthotopic esophageal cancer mouse model, decreased tumor growth and lung metastasis with reduced Ki-67 and phospho-STAT3 expression were observed in mice treated with CYT-Rx20. Together, our results suggest that CYT-Rx20 is a potential β-nitrostyrene-based anticancer compound against the tumor growth and metastasis of esophageal cancer.

This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI). ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract), and the control was reverse osmosis pure water (RO water). One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001). With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05). Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study suggests that zinc can be used as supplements in cancer patients receiving radiotherapy to reduce radiation-induced complications.

Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens. Our developmental biology studies identified defects in feather medulla formation, and physical studies revealed that the frizzle feather curls in a stepwise manner. The frizzle gene is transmitted in an autosomal incomplete dominant mode. A whole-genome linkage scan of five pedigrees with 2678 SNPs revealed association of the frizzle locus with a keratin gene-enriched region within the linkage group E22C19W28_E50C23. Sequence analyses of the keratin gene cluster identified a 69 bp in-frame deletion in a conserved region of KRT75, an α-keratin gene. Retroviral-mediated expression of the mutated F cDNA in the wild-type rectrix qualitatively changed the bending of the rachis with some features of frizzle feathers including irregular kinks, severe bending near their distal ends, and substantially higher variations among samples in comparison to normal feathers. These results confirmed KRT75 as the F gene. This study demonstrates the potential of our approach for identifying genetic determinants of feather forms.