Diabetes Mellitus as Cancer Risk: A 14-year, Cross-Sectional Analysis.

Diabetes mellitus is widely thought to be a risk factors of cancers, but evidence of the association remains inconclusive, especially in Asian countries where few relevant studies have been conducted. Our study aimed to estimate overall and specific types of cancer risks among diabetes patients in Southern Thailand. Patients diagnosed with diabetes who visited the outpatient clinic of Songklanagarind Hospital during 2004 to 2018 were included. Newly diagnosed cancer patients were identified using the hospital-based cancer registry. Age-standardized incidence ratios (ASRs) and standardized incidence ratios (SIRs) were used to estimate and compare the cancer risks among diabetes patients and the general population in Southern Thailand. Of 29,314 diabetes patients identified during the study period, 1,113 patients had developed cancer. An increased risk for overall cancer was observed in both genders, with SIRs [95% CI] of 2.99 [2.65, 3.39] in men and 3.51 [3.12, 3.96] in women. Increases in the risk of several site-specific cancers including liver cancer, non-melanoma skin cancer, colon cancer and lung cancer in both sexes; prostate cancer, lymphoid leukemia, and multiple myeloma in men; and endometrial, breast, and thyroid cancer in women were observed. Our study found that diabetes generally increased the risk of both overall and site-specific cancers.

Factors influencing precautions against antineoplastic drug exposure among nurses and nurse assistants in Thailand.

BACKGROUND: Antineoplastic drugs (AD) are important chemical risks for healthcare workers. Precautions against AD exposure include the use of appropriate personal protective equipment (PPE). Evaluation of PPE usage during patient care processes has not been reported in Thailand. We aimed to evaluate the level of PPE usage and factors predicting PPE usage among nurses and nurse assistants in Thailand. METHODS: A cross-sectional survey was conducted in a university hospital and two general hospitals. The questionnaires covered demographic characteristics, self-reported use of PPE and 7 predictive factors. Mixed-effects modeling was used to determine the association between standardized score of predictive factors and PPE usage score. RESULTS: The response rate was 78.6% and 884 participants were left for analysis after data cleaning. Among nurses (n = 499), higher PPE usage score was associated with self-efficacy (ß = 0.28, 95% CI 0.21, 0.34), workplace safety climate (ß = 0.27, 95% CI 0.20, 0.34), and conflict of interest (ß = - 0.07, 95% CI - 0.14, - 0.01). Among nurse assistants (n = 385), higher PPE usage score was associated with self-efficacy (ß = 0.27, 95% CI 0.18, 0.36), interpersonal influence (ß = 0.14, 95% CI 0.04, 0.24), workplace safety climate (ß = 10.29, 95% CI 0.19, 0.38), and conflict of interest (ß = - 0.14, 95% CI - 0.24, - 0.03). CONCLUSIONS: Several factors were associated with PPE usage among nurses and nurse assistants. Improved PPE usage against AD can be promoted through interventions that modify those factors.

Significance of Pretreatment Hemoglobin-Albumin-Lymphocyte-Platelet Index for the Prediction of Suboptimal Surgery in Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) is the leading cause of death in gynecological cancers in developed countries. In recent years, there has been a growing need for economical and accurate pretreatment laboratory investigations to assess the prognosis of patients with advanced EOC (AEOC). We aimed to investigate the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) index in suboptimal cytoreduction and oncological outcomes. Methods: A prognostic prediction model for diagnosing suboptimal cytoreduction for patients with AEOC receiving neoadjuvant chemotherapy (NACT) was developed. Multivariate logistic regression analysis was performed to identify the independent predictors of suboptimal cytoreduction, with a P-value < 0.05, and then transformed into risk-scoring systems. Internal validation was performed using the bootstrapping procedure, and predictive cytoreduction (PSC) scores were compared using non-parametric receiver operating characteristic (ROC) regression. Survival analysis was performed using Kaplan-Meier estimation and Cox proportional regression. Results: In total, 473 patients were analyzed, and the rate of suboptimal surgery was 43%. A scoring system in predicting suboptimal cytoreduction included age, cancer antigen (CA)-125 level before surgery, performance status, cycles of chemotherapy, peritoneal cancer index, and HALP index ≤ 22.6. The model had good discriminative ability (area under the ROC (AUROC), 0.80; 95% confidence interval (CI), 0.76 - 0.84), outperforming the PSC score (AUROC, 0.75; 95% CI, 0.71 - 0.80). The score was divided into the low-risk (positive predictive value (PPV), 22.4; 95% CI, 17.8 - 27.7), moderate-risk (PPV, 65.9; 95% CI, 56.9 - 74.0), and high-risk (PPV, 90.6; 95% CI, 79.3 - 96.9) groups. The HALP index score of ≤ 22.6 was independently associated with progression-free survival (hazard ratio (HR), 2.92; 95% CI, 1.58 - 5.40) and overall survival (HR, 2.66; 95% CI, 1.57 - 4.49). Conclusion: The HALP index is a newly predicted factor for suboptimal cytoreduction and oncological outcomes in patients with AEOC after NACT.

Differential Abundances of Bdellovibrio and Rheinheimera in the Oral Microbiota of Neonates With and Without Clinical Sepsis.

BACKGROUND: Neonatal sepsis is associated with high rates of morbidity and mortality, long hospital stays and high cost of care, thereby inflicting a burden on health care systems. Oral care with breast milk has been shown to modify the intestinal tract microbiota and immune system. Herein, we attempted to identify probiotics that may be beneficial to prevent or treat neonatal sepsis. METHODS: This was a secondary analysis comparing the microbiota during oropharyngeal care in very-low-birth-weight infants with and without clinical sepsis. Oral samples were collected before oral feeding was initiated. The primary outcome was oral microbiota composition including diversity, relative abundance and linear discriminant analysis effect size. RESULTS: Sixty-three neonates, including 39 and 24 with and without clinical sepsis, respectively, were enrolled. The medians gestational age and birth weight were 29 (27-30) weeks and 1010 (808-1263) g. Neonates with clinical sepsis had lower gestational age, birth weight (both P < 0.001) and lower rate of oral care with breast milk ( P = 0.03), but higher doses and days of antibiotic exposure (both P < 0.001) compared to neonates without clinical sepsis. No differences in alpha and beta diversities were found between groups and Streptococcus agalactiae was the most common bacteria in both groups. Linear discriminant analysis effect size analysis revealed that neonates without clinical sepsis had significantly higher abundances of order Bdellovibrionales, family Bdellovibrionaceae, genus Bdellovibrio and genus Rheinheimera . CONCLUSIONS: Neonates without clinical sepsis had a significantly greater abundance of the Bdellovibrio and Rheinheimera genera.

HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients. METHODS: The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance. RESULTS: The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively). CONCLUSION: Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Factors associated with the worsening of COVID-19 symptoms among cohorts in community- or home-isolation care in southern Thailand.

Introduction: This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial. Methods: A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral. Results: Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group. Discussion: These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.

Mutations of fibroblast growth factor receptor 3 gene (FGFR3) in transitional cell carcinoma of urinary bladder in Thai patients [Revision-2a].

OBJECTIVE: Determine the incidence of FGFR3 mutations in Thai patients with bladder transitional cell carcinoma (TCC), and evaluate their correlation with pathological characteristics. MATERIAL AND METHOD: One hundred twenty two frozen tissue samples from TCC patients were analyzed for mutations in exons 7, 10, and 15 of FGFR3 by polymerase chain reaction and direct DNA sequencing. RESULTS: FGFR3 mutations were detected in 22 of 122 cases (18%) studied, all of which were found within previously identified hotspots, including S249C (13 cases; 59%) and R248C (4 cases; 18%) in exon 7, and Y375C (5 cases; 23%) in exon 10, but no mutations in exon 15. Sixty-five patients (53%) were categorized as non-muscle-invasive TCC (pTa-pT1). The incidence of mutations is significantly higher in non-muscle-invasive tumors (28%) compared to the muscle-invading group (7%) (p < 0.01). Patients with grade (G) 1 TCC have significantly higher mutation frequency (40%) compared to other grades (4%) (p < 0.01). When T stage and grade were considered together, mutations were most commonly found in Ta-T1/G1 TCC (18/45 cases, 40%). Mean follow-up period was 45.1 months. Two-year and four-year overall survival (OS) was 70% and 56% respectively. Three-year OS in non-muscle-invasive TCC (80%) is significantly higher than that of muscle invading TCC (41%) (p < 0.01). However three-year OS in cases with an FGFR3 mutation (73%) is not significantly different from cases without a mutation (61%). In 16 cases with an FGFR3 mutation and recurrent disease, no mutations were detected in metachronous disease. CONCLUSION: The overall incidence of FGFR3 mutations in Thai patients with TCC was lower than similar reports from other ethnic groups. In the presented cases, although FGFR3 mutations were frequently detected in low-grade, non-muscle-invasive TCC, identical mutation was not conserved in metachronous disease, thereby precluding the use of this marker in detection of tumor recurrence.

Long Duration of Oral Care Using Mother's Own Milk Influences Oral Microbiota and Clinical Outcomes in Very-low-birthweight Infants: Randomized Controlled Trial.

BACKGROUND: Several studies have focused on the clinical outcomes of oral care using colostrum for a limited time (2-5 days) in very-low-birthweight (VLBW) infants. However, the effect of long-term mother's own milk (MOM) on the clinical outcomes and oral microbiota of VLBW infants remains unknown. METHODS: In this randomized controlled trial, VLBW neonates were randomly assigned to oral care by MOM or sterile water (SW) groups until they started oral feeding. The primary outcome was oral microbiota composition including alpha and beta diversity, relative abundance, and linear discriminant analysis effect size (LEfSe). The secondary outcomes were various morbidities and mortality. RESULTS: The baseline characteristics of the two groups did not differ (63 neonates, MOM group, n = 30, oral care 22 days; SW group, n = 33, oral care 27 days). There was no significant difference in alpha and beta diversities between the groups before and after the intervention. The MOM group had a significantly lower rate of clinical sepsis than the SW group (47% vs. 76%, risk ratio = 0.62, 95% CI: 0.40-0.97). The relative abundance of Bifidobacterium bifidum and Faecalibacterium were maintained after MOM care, especially in neonates without clinical sepsis, but decreased after SW care. LEfSe showed that neonates in the MOM and SW groups with clinical sepsis had the highest abundance of Pseudomonas and Gammaproteobacteria, respectively, compared with neonates without sepsis. CONCLUSIONS: A longer duration of oral care using MOM in VLBW infants sustains healthy bacteria and decreases the risk of clinical sepsis.

Immunohistochemistry-based molecular subtyping of triple-negative breast cancer and its prognostic significance.

Background: Immunohistochemistry (IHC)-based protein markers representing molecular subtypes are of great value for routine use. This study aimed to evaluate the frequency distributions of the molecular subtypes of triple-negative breast cancer (TNBC) using IHC-based surrogate markers and examined their prognostic value. Methods: Patients with TNBC treated at a university hospital in Southern Thailand were included in this study. Expression levels of androgen receptor, CD8, Forkhead box transcription factor C1, and Doublecortin-like kinase 1 were detected in tumor tissue to classify them into luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymal-like (MES), and unclassifiable (UC) subtypes. The association between variables and disease-free survival (DFS) and overall survival (OS) was analyzed using Cox proportional hazards regression. Results: Among the 195 cases of TNBC, the frequency distribution of the IHC-based subtype was as follows: BLIS, 52.8%; LAR, 19.0%; IM, 17.4%; MES, 0.5%; and un-classifiable, 10.3%. BLIS subtype was significantly found in younger ages (mean: 49.6 years) than other subtypes (mean: 51-57.7 years). LAR and BLIS subtypes were significantly associated with poorer OS compared to the IM subtype in univariate analysis, however, only BLIS was significant in multivariate analysis (HR: 3.29, 95% CI: 1.01-10.72). IHC-based subtype was not found to be associated with DFS. Conclusion: This study revealed the differences in the proportion frequency of IHC-based TNBC subtypes in Thai patients compared to other populations. IHC-based molecular subtyping may be beneficial for prognosis. However further refinement of the molecular classification of TNBC is needed for better clinical relevance.

Predictive and Prognostic Value of TUBB3, RRM1, APE1, and Survivin Expression in Chemotherapy-Receiving Patients with Advanced Non­Small Cell Lung Cancer.

BACKGROUND: This study aimed to evaluate the expression of class III ß-tubulin (TUBB3), ribonucleoside-diphosphate reductase 1 (RRM1), apurinic/apyrimidinic endonuclease 1 (APE1), and survivin in patients with advanced non-small cell lung cancer (NSCLC) to predict response to chemotherapy. METHODS: TUBB3, RRM1, APE1, and survivin expression levels were determined using immunohistochemistry. Protein expression was validated in Car/Pac-resistant human H1792 and A549 cells. This study included 86 patients, among whom 34 received cisplatin (Cis)/gemcitabine (Gem) and 52 received carboplatin (Car)/paclitaxel (Pac). RESULTS: Patients with low TUBB3 expression and high RRM1 and survivin expression had higher response rates than those with low RRM1 and survivin expression and high TUBB3 expression in the Car/Pac regimen. The multivariate analysis indicated that TUBB3 and RRM1 were significant independent predictive biomarkers for the Car/Pac regimen; however, there was no association between any protein and overall response in patients treated with this regimen. In the Cis/Gem regimen, only high TUBB3 expression was associated with poor overall survival; however, it did not exhibit a prognostic ability. CONCLUSION: The expression levels of TUBB3 and RRM1 in NSCLC cells are potential predictive biomarkers, but not prognostic factors, of response to chemotherapy in patients with NSCLC receiving the Car/Pac regimen.

Binary semantic segmentation for detection of prostate adenocarcinoma using an ensemble with attention and residual U-Net architectures.

An accurate determination of the Gleason Score (GS) or Gleason Pattern (GP) is crucial in the diagnosis of prostate cancer (PCa) because it is one of the criterion used to guide treatment decisions for prognostic-risk groups. However, the manually designation of GP by a pathologist using a microscope is prone to error and subject to significant inter-observer variability. Deep learning has been used to automatically differentiate GP on digitized slides, aiding pathologists and reducing inter-observer variability, especially in the early GP of cancer. This article presents a binary semantic segmentation for the GP of prostate adenocarcinoma. The segmentation separates benign and malignant tissues, with the malignant class consisting of adenocarcinoma GP3 and GP4 tissues annotated from 50 unique digitized whole slide images (WSIs) of prostate needle core biopsy specimens stained with hematoxylin and eosin. The pyramidal digitized WSIs were extracted into image patches with a size of 256 × 256 pixels at a magnification of 20×. An ensemble approach is proposed combining U-Net-based architectures, including traditional U-Net, attention-based U-Net, and residual attention-based U-Net. This work initially considers a PCa tissue analysis using a combination of attention gate units with residual convolution units. The performance evaluation revealed a mean Intersection-over-Union of 0.79 for the two classes, 0.88 for the benign class, and 0.70 for the malignant class. The proposed method was then used to produce pixel-level segmentation maps of PCa adenocarcinoma tissue slides in the testing set. We developed a screening tool to discriminate between benign and malignant prostate tissue in digitized images of needle biopsy samples using an AI approach. We aimed to identify malignant adenocarcinoma tissues from our own collected, annotated, and organized dataset. Our approach returned the performance which was accepted by the pathologists.

The prognostic value of p53, Bcl-2 and Bax expression in laryngeal cancer.

OBJECTIVE: Determine the prognostic value of p53, Bcl-2 and Bax expression in cancer of the larynx. MATERIAL AND METHOD: Ninety-four patients diagnosed with laryngeal squamous cell carcinoma were analyzed for 5-year overall survival in relation to immunohistochemical expression of p53, Bcl-2, and Bax proteins. RESULTS: The present study included 86 males and eight females with a mean age of 65.1 years. Half of the patients (51%) were in stages III and IV. Radiation (44.7%) and radiation plus surgery (40.4%) were the main treatments. The frequency of p53, Bcl-2, and Bax expression was 58.1%, 18.5%, and 87.2%, respectively. The 5-year overall survival rate was 49.7%. Univariate analysis revealed that T-stage, N-stage and treatment were significantly associated with 5-year overall survival. In the multivariate Cox regression, T-stage, treatment, and Bcl-2 expression were significantly associated with survival. Positive Bcl-2 expression was associated with better survival (Hazard ratio 0.23, 95% CI 0.06-0.81). CONCLUSION: The positive Bcl-2 expression is an independent prognostic marker in laryngeal squamous cell carcinoma.

Expression and Prognostic Significance of c-Myc, ALK, ROS1, BRAF, and PD-L1 Among Patients With Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer death worldwide, for which better knowledge in molecular prognostic factors is needed to improve clinical outcome. This study aimed to investigate the clinical significance of c-Myc, ALK, ROS1, BRAF, and PD-L1 in NSCLC patients. Methods: Formalin-fixed paraffin-embedded tissue specimens were obtained from 124 NSCLC patients. Of these, 66 matched specimens of normal respiratory epithelial and tumor tissue from patients with stages I-III, who underwent surgical resection, and 58 NSCLC specimens from stage IV patients were recruited into this analysis. Immunohistochemistry staining along with semiquantitative criteria were used to evaluate the expression of the interested proteins. Results: Of the 66 patients with stages I-III, positive expression of c-Myc was detected in 12 specimens (18.2%) of NSCLC tissue, whereas none of the normal respiratory epithelial tissue was found to have c-Myc expression (P < .001). Of the 66 NSCLC patients, 28 (43.8%) had PD-L1-positive staining on 1%-49% tumor cells and 7 (10.9%) patients expressed PD-L1 in ⩾50% tumor cells. One (2.3%) adenocarcinoma patient was found to have ROS1 rearrangement. Patients with no expression of c-Myc and PD-L1 (co-negative expression) tended to have a better prognosis than other subgroups. Conclusions: NSCLC tissue significantly expressed more c-Myc and PD-L1, compared with the matched normal respiratory epithelium, emphasizing the important role of these key drivers in tumorigenesis. Therapeutic approach to precisely inhibit the targetable molecular pathways should be considered on an individual patient basis to improve survival outcome.

Copy number gains of chromosome 17 identified by dual in situ hybridization in non-small cell lung cancer tissue correlate with overexpression of c-Myc.

Background: c-Myc regulates multiple genes involved in cell proliferation in various cancer types including non-small cell lung cancer (NSCLC). Copy number gains of cytoband 17q25.3, along with chromosome 17, have been reported in NSCLC patients, emphasizing the clinical significance as a potential molecular target for therapy. The upregulation of c-Myc has been found to accelerate tumor development associated with duplication of the syntenic human cytoband 17q25.3. This study aimed to explore and compare the correlations of chromosome 17 copy number and c-Myc expression in NSCLC with the paired-normal respiratory epithelium and to examine their role as potential molecular targets for NSCLC therapy. Methods: A total of 66 NSCLC tissue samples with paired-normal respiratory epithelium were examined. The copy number of chromosome 17 was determined by human epidermal growth factor receptor 2 (HER2)/centromeric enumeration probe of chromosome 17 (CEP17) dual in situ hybridization (DISH). Results: Copy number gains of chromosome 17 were identified in 8 of 60 (13.3%) available NSCLC specimens. No copy number gains of chromosome 17 were demonstrated in the paired-normal respiratory epithelium. The mean HER2 (1.2±0.3) and CEP17 (1.4±0.3) copy numbers of the normal respiratory epithelium were significantly lower than those of the NSCLC tissue [1.8±1.0 vs. 2.0±0.8, respectively (P<0.001)]. Twelve of 66 (18.2%) NSCLC patients had overexpression of c-Myc. Five (41.7%) of the patients whose tumors positive for c-Myc had HER2 gene amplification [1] or copy number gain of chromosome 17 [4]. HER2 gene amplification or copy number gain of chromosome 17 and high expression of c-Myc were associated with decreased overall survival. Conclusions: Both biomarkers deserve further investigation to identify NSCLC patients with poorer survival outcomes requiring better therapeutic approaches.

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand.

BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC. METHODS: Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations. RESULTS: The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations. CONCLUSIONS: The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Diagnostic and prognostic value of serum miR-145 and vascular endothelial growth factor in non-small cell lung cancer.

Previous studies have reported the diagnostic and prognostic value of serum microRNA (miR)-145 and vascular endothelial growth factor (VEGF) levels in various types of cancer; however, their clinical use in non-small cell lung cancer (NSCLC) remains unclear. The present study included 215 patients, 106 with NSCLC and 109 with other lung diseases (OLDs). miR-145 expression levels were determined using reverse transcription-quantitative PCR (RT-qPCR) and VEGF levels were measured using an ELISA. The diagnostic performance was assessed using a receiver operating characteristic curve and area under the curve (AUC) analysis. A Kaplan-Meier survival curve and Cox regression analysis were employed to evaluate the prognostic significance of the markers. The biological function of miR-145 was examined in A549 and H1792 cell lines. The effects of miR-145 on cell proliferation of NSCLC cells were evaluated by flow cytometry, and the expression levels of miR-145 and cell cycle-related genes were determined by RT-qPCR. The results revealed that miR-145 and VEGF exhibited fair diagnostic performance [AUC, 0.61 (95% CI, 0.55-0.68) and AUC, 0.64 (95% CI, 0.57-0.71), respectively]. Combining age and smoking status with miR-145 and VEGF provided the best model for differentiating patients with NSCLC from those with OLDs (AUC, 0.76; 95% CI, 0.69-0.83). Furthermore, low serum miR-145 levels were associated with poor overall survival [hazard ratio (HR), 0.48; 95% CI, 0.27-0.85], whereas high VEGF levels were not associated with poor overall survival (HR, 1.47; 95% CI, 0.81-2.68). In addition, the results of the in vitro experiments indicated that miR-145 decreased cell proliferation via the induction of cell cycle arrest. In conclusion, the findings of the present study suggested that combining miR-145 and VEGF levels with clinical risk factors may be a potential diagnostic scheme for NSCLC. In addition, serum miR-145 may be used as a prognostic marker. These results indicated that miR-145 may function as a tumor suppressor in NSCLC.

Cancer survival in Thailand from 1997 to 2012: Assessing the impact of universal health coverage.

BACKGROUND: In recent decades, many countries worldwide have implemented some form of Universal Health Coverage (UHC). We sought to evaluate incidence and survival trends of breast, cervical, and colorectal cancer before and after the implementation of UHC in Thailand. METHODS: The age-standardized incidence rate and 1- and 5-year net survival (NS) were calculated for five Thai provinces, namely Bangkok, Chiang Mai, Khon Kaen, Lampang, and Songkhla for breast, cervix, and colorectal cancer in three study periods (1997-2012): before, during, and after the implementation of UHC. RESULTS: The incidence of breast and colorectal cancer has increased over time, while the incidence of cervical cancer has decreased (17.9-29.9, 9.0-13.6, and 19.6-12.3 per 100,000, respectively). Larger proportion of breast cancer were diagnosed with localized stage after UHC implementation compared to the period prior to UHC (31.5 % vs 19.0 %). Overall, The improvement in survival by cancer site varied in magnitude with a 5-year NS increase from 61.3 % to 75.1 % for breast, 55.4-59.5 % for cervical, and 39.9-47.6 % for colorectal cancer. The amount of increase slightly differed across provinces. CONCLUSION: Rising incidence for breast and colorectal, and declining cervical cancer may partly be attributable to improved awareness and early detection programs. Additionally, improvement in survival may partly be attributable to increased access to healthcare, availability of treatment, and increased access to cancer screening after UHC was implemented. Thus, continued expansion of UHC package on cancer could potentially contribute to further improvement of cancer control in Thailand. POLICY SUMMARY: This study provides important evidence on the impact of UHC in cancer burden and survival for breast, cervical, and colorectal cancer in Thailand. This study serves as an example for other countries where UHC has been recently implemented and guide policymakers in allocating resources towards UHC and cancer control programs.

Serum Proteomic Profiling Reveals Differentially Expressed IGHG3 and A1AG1 as Potential Predictors of Chemotherapeutic Response in Advanced Non-small Cell Lung Cancer.

BACKGROUND: This study aimed to identify differentially expressed proteins in the serum of advanced non-small cell lung cancer (NSCLC) patients responding to carboplatin (CAR) plus paclitaxel (PTX) chemotherapy compared to non-responders. MATERIALS AND METHODS: Serum from 8 responders and 6 non-responders was subjected to proteomic analysis by label-free liquid chromatography tandem mass spectrometry and validated by western blotting. CAR/PTX-resistant human H1792 and A549 cells were used for evaluating gene expression. RESULTS: Fifty-two proteins were differentially expressed between responders and non-responders. Alpha 1 antitrypsin antibody, alpha 1 acid glycoprotein (A1AG1), afamin, protein S100-A9 and immunoglobulin heavy constant gamma 3 (IGHG3) were validated. IGHG3 was elevated (p=0.037) while A1AG1 was reduced (p=0.003) in responders as compared to non-responders. Gene expression of IGHG3 and ORM1 in resistant cells showed consistent results with the proteomics profiles. CONCLUSION: Serum expression levels of IGHG3 and A1AG1 proteins may be useful to recruit an NSCLC subpopulation that can benefit from CAR plus PTX standard therapy.

Epithelial-Mesenchymal Transition Predicts Survival in Oral Squamous Cell Carcinoma.

Synergistic loss of E-cadherin and acquisition of vimentin are characteristic feature of epithelial-mesenchymal transition (EMT) which confers an invasive phenotype of epithelial cancer cells. The aim of the study was to evaluate the prognostic significance of E-cadherin and vimentin expression individually and in combination as a measure of epithelial-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Expression of E-cadherin and vimentin through immunohistochemical analysis was examined in 200 patients with surgically resected OSCC. Combined E-cadherin and vimentin expression was evaluated to determine the EMT status. Kaplan-Meier curves and log-rank test were used to compare differences in survival. Cox regression analysis was performed to identify independent prognostic factors. E-cadherin expression was negative in 28 (14%) tumors, and vimentin expression was positive in 87 (43.5%) tumors. Moreover, 99 (49.5%), 87 (43.5%), and 14 (7.5%) tumors exhibited no, partial, and complete EMT, respectively. Both individual protein expression were significant prognostic factors [Negative E-cadherin, hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.04-2.93; positive vimentin, HR = 1.64, 95% CI = 1.12-2.41]. For EMT status, the HR increased with EMT progression [partial EMT, HR = 1.64, 95% CI = 1.09-2.49; complete EMT, HR = 2.88, 95% CI = 1.44-5.79], of which, the complete EMT had higher HR than was individual protein expression. Combined E-cadherin and vimentin expression as a measure of EMT showed a superior prognostic significance compared with individual protein expression.

Serum miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer.

Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor ß (TGF-ß)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-ß concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer.