Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.
From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.
Purpose: Abdominal migraine (AM) is a very common functional gastrointestinal disorder in children. This study reports the clinical features and response of AM to prophylactic treatment in children. Methods: This retrospective study was conducted between January 2010 and December 2019 at the Royal Hospital in the Sultanate of Oman. This study included children aged ≤ 13 years with a diagnosis of AM based on the Rome IV criteria for functional diagnoses. Clinical, demographic, and treatment data were collected. Results: Seventy-four children were identified, of which 43 were eligible for inclusion in this study. The median age at the onset of symptoms was 7 years (range, 2-12 years). The most frequent symptoms were headache (81.4%), nausea (79.1%), and vomiting (72.1%). Of the total cohort, 46.5%, 23.3%, and 6.9% received riboflavin, pizotifen, and propranolol monotherapy, respectively. Combination therapy was also used; 16.3% of children received pizotifen and propranolol, 4.7% received riboflavin and pizotifen, and 2.3% received riboflavin and propranolol. Patients treated with propranolol monotherapy showed 100% clinical improvement and those treated with riboflavin or pizotifen monotherapy showed 90% clinical improvement. Response to combination therapy with pizotifen and propranolol was 71.4%, and with riboflavin and pizotifen was 100%. In addition, treatment response was significantly associated with the presence of vomiting (p=0.039). Conclusion: We found a favorable response to various modalities and combination treatments with riboflavin, pizotifen, and propranolol in children with AM. In addition, the presence of vomiting may predict treatment response.
Blood eosinophil counts have emerged as a chronic obstructive pulmonary disease (COPD) biomarker that predict the effects of inhaled corticosteroids (ICS) in clinical practice. Post-hoc and prospective analysis of randomized control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to ICS. COPD patients with frequent exacerbations (2 or more moderate exacerbations/yr) or a history of hospitalization have a greater response to ICS. Ex-smokers also appear to have a greater ICS response. Blood eosinophil counts can be combined with clinical information such as exacerbation history and smoking status to enable a precision medicine approach to the use of ICS. Higher blood eosinophil counts are associated with increased eosinophilic lung inflammation, and other biological features that may contribute to the increased ICS response observed. Emerging data indicates that lower blood eosinophil counts are associated with an increased risk of bacterial infection, suggesting complex relationships between eosinophils, ICS response, and the airway microbiome.
In this paper, the authors intended to summarize briefly the features of lymphoma with regard to $^{18}F$-FDG PET for assessment of tumor response to therapy, to describe why assessment of treatment response should be performed, to review what method so far has been used in monitoring treatment response, to discuss what limitations of morphologic imaging criteria for assessing tumor response are, in compared with $^{18}F$-FDG PET, and to introduce recently proposed criteria for assessing tumor response in malignant lymphoma. And also the authors emphasize the need to understand the characteristics of diagnostic performance of $^{18}F$-FDG PET in several clinical settings in order to interpret $^{18}F$-FDG PET results appropriately, and to encourage the use of interval likelihood ratio to enhance clinical implications of test results which, in turns, allows referring physicians to understand the meaning of interpretation with easy. Until recently, treatment response has been assessed according to the morphologic criteria. Metabolic imaging with $^{18}F$-FDG PET was adopted to have important role for treatment assessment in IWC+PET criteria proposed recently by IHP. To accomplish this role, we should perform and interpret $^{18}F$-FDG PET according to IWC+PET criteria. It is important for referring physicians to understand the various limitations of $^{18}F$-FDG PET and pitfalls in PET interpretation, and to understand that clinical information are needed by nuclear medicine physicians to optimize the interpretation of $^{18}F$-FDG PET.
Objective: Microarray data were analyzed to explore key genes and their functions in progression of colorectal cancer (CRC). Methods: Two microarray data sets were downloaded from Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified using corresponding packages of R. Functional enrichment analysis was performed with DAVID tools to uncover their biological functions. Results: 631 and 590 DEGs were obtained from the two data sets, respectively. A total of 32 common DEGs were then screened out with the rank product method. The significantly enriched GO terms included inflammatory response, response to wounding and response to drugs. Two interleukin-related domains were revealed in the domain analysis. KEGG pathway enrichment analysis showed that the PPAR signaling pathway and the renin-angiotensin system were enriched in the DEGs. Conclusions: Our study to systemically characterize gene expression changes in CRC with microarray technology revealed changes in a range of key genes, pathways and function modules. Their utility in diagnosis and treatment now require exploration.
Mayaki, Abubakar Musa;Razak, Intan Shameha Abdul;Adzahan, Noraniza Mohd;Mazlan, Mazlina;Rasedee, Abdullah
Journal of Veterinary Science
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제21권6호
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pp.82.1-82.10
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2020
Background: The clinical presentation of horses with back pain (BP) vary considerably with most horse's willingness to take part in athletic or riding purpose becoming impossible. However, there are some clinical features that are directly responsible for the loss or failure of performance. Objectives: To investigate the clinical features of the thoracolumbar region associated with BP in horses and to use some of the clinical features to classify equine BP. Methods: Twenty-four horses comprised of 14 with BP and 10 apparently healthy horses were assessed for clinical abnormality that best differentiate BP from normal horses. The horses were then graded (0-5) using the degree of pain response, muscular hypertonicity, thoracolumbar joint stiffness and overall physical dysfunction of the horse. Results: The common clinical features that significantly differentiate horses with BP from non-BP were longissimus dorsi spasm at palpation (78.6%), paravertebral muscle stiffness (64.3%), resist lateral bending (64.3%), and poor hindlimb impulsion (85.7%). There were significantly (p < 0.05) higher scores for pain response to palpation, muscular hypertonicity, thoracolumbar joint stiffness and physical dysfunction among horses with BP in relation to non-BP. A significant relationship exists between all the graded abnormalities. Based on the cumulative score, horses with BP were categorized into mild, mild-moderate, moderate and severe cases. Conclusions: BP in horse can be differentiated by severity of pain response to back palpation, back muscle hypertonicity, thoracolumbar joint stiffness, physical dysfunctions and their cumulative grading score is useful in the assessment and categorization of BP in horses.
This study was conducted to investigate the combined effects of VFA composition of rumen fluid and heat exposure (30${\pm}$2$^{\circ}C$) on the general clinical view and insulin secretory response to glucose in sheep. The total infusion of nutrients was examined in sheep via the technique of continuous alimentation. Four adult Suffolk sheep fitted with a permanent ruminal cannula and a simple T-shaped duodenal cannula were used. A peristaltic pump was used to infuse the solutions of volatile fatty acid triglycerides (VFA-TG) consisting of 70 triacetin : 20 tripropionin : 10 tributyrin (low propionin division: LP) and 50 triacetin : 40 tripropionin : 10 tributyrin (high propionin division: HP) on the basis of energy and minerals into the rumen, and casein solution into the duodenum. The effects of heat exposure and type of the levels of VFA-TG solutions on the insulin secretory response to glucose in sheep were investigated by using hyperglycemic clamp (HGC) technique. The results obtained are summarized as follows: 1. During the heat exposure (latter half of the infusion period), respiration rate, heart rate and rectal temperature increased (P<0.01, P<0.01, P<0.05), but the levels of VFA-TG solutions (LP and HP division) did not affect the general clinical view except for the heart rate. 2. In the HGC technique, glucose infusion rate (GIR) and mean plasma insulin increments (MPII) tended to be ower in the heat exposure than in the thermoneutral environment, but no significant difference was found among the treatments. GIR and MPII remained unchanged between the levels of VFA-TG solutions. 3. In the HGC technique, ratio of MPII to GIR (MPII/GIR) which represents pancreatic ${\beta}$-cell response to glucose stimulation remained unchanged among the treatments.
Khokher, Samina;Qureshi, Muhammad Usman;Mahmood, Saqib;Nagi, Abdul Hannan
Asian Pacific Journal of Cancer Prevention
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제14권5호
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pp.3223-3228
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2013
Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.
Purpose: We aimed to investigate the efficacy and safety of adalimumab in pediatric-onset Crohn's disease patients who had failed treatment with infliximab. Methods: In this retrospective study, patients included were those who had been diagnosed with Crohn's disease before 18 years old, and had received treatment with adalimumab after infliximab failure. The efficacy of adalimumab treatment was investigated at 1 month and 1 year, and adverse events that had occurred during treatment with adalimumab were explored. Results: Ten patients were included in this study. The median duration from diagnosis to adalimumab treatment was 5.5 years (range: 2.4-7.9 years). At 1 month after adalimumab initiation, 80% (8/10) of patients showed clinical response, and 40% (4/10) achieved clinical remission. At 1 year, 71% (5/7) of patients showed clinical response, and 43% (3/7) were under clinical remission. Among the total included patients, 5 patients (50%) showed clinical response at 1 year. Primary non-response to adalimumab was observed in 2 patients (20%), and secondary failure to adalimumab was observed in 3 patients (30%) during 1 year treatment with adalimumab. No serious adverse event had occurred during adalimumab treatment. Conclusion: Adalimumab was effective for 1 year without serious adverse events in half of pediatric-onset Crohn's disease patients who had failed treatment with infliximab.
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