Significant Association of Antiepileptic Drug Polytherapy with Decreased FT4 Levels in Epileptic Patients.

Epileptic patients have to continue anti-epileptic drugs (AED) over a long period of time which can have deleterious effects on the endocrine system including the thyroid hormones with rare check. Risk factors for the development of thyroid dysfunction are still unclear. Therefore the aim of study was to evaluate thyroid functions in epileptic patients receiving anti-epileptic drugs (AED) as monotherapy and polytherapy and to determine potential risk of low thyroid function in epileptic patients receiving treatment. This cross-sectional study included 100 epilepsy patients more than 12 years of age. Serum levels of free thyroxin (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were evaluated in all subjects in addition to serum AED levels. TSH levels were found to be significantly higher in the polytherapy subgroup (p < 0.05) in comparison to the monotherapy group. 44% of the patients in the VPA monotherapy group had raised TSH levels and 41.2% of the patients on CBZ had low FT4. A significant negative correlation was observed between CBZ and FT4 (p < 0.05). Female sex and old age were additional risk factors detected for deranged thyroid function. Female patients with epilepsy, an older age and AED polytherapy were found to be associated with a higher risk of thyroid dysfunction. Thus, Thyroid function in these patients should be monitored closely. In conclusion, we observed significant changes in thyroid hormone levels in patients receiving antiepileptic treatment in both monotherapy and polytherapy. Elevated CBZ levels were significantly associated with decreased FT4 levels.

Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis - a preliminary study.

AIM: To investigate the correlation between the concentration of active-matrix metalloproteinases-9 (aMMP-9) in pulpal blood and the outcome of pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis (SIP). METHODOLOGY: Forty permanent molar teeth with a clinical diagnosis of SIP and normal apical tissues with periapical index (PAI) score ≤ 2 and ten permanent teeth (8 molars and two premolars) with a diagnosis of normal pulp that required root canal treatment for prosthetic reasons from patients between the ages of 15-35 years were recruited. All clinical procedures were performed under local anaesthesia and rubber dam isolation. After access opening, the coronal pulp tissue was amputated up to the canal orifice. A 100 µL volume of the pulpal blood was collected using a micropipette and transported to the laboratory. Sodium hypochlorite (2.5 %) was used as a haemostatic agent, and mineral trioxide aggregate (MTA) was used as the pulp capping material. The tooth was restored with composite at the same visit. Teeth with normal pulps were treated with single-visit root canal treatment. Patients with pulpotomy were recalled at 6 and 12 months. Outcome assessment of teeth with pulpotomy was carried out at 12 months and was categorized as success (asymptomatic patients with PAI score ≤ 2) or failure (symptomatic patients or PAI score ≥ 3). Quantification of aMMP-9 in pulpal blood was achieved using a fluorometric assay. The following statistical analyses were performed to assess the data: t-test, Fisher's exact test, kappa coefficient, non-parametric test, Wilcoxon rank-sum test, Spearman rank correlation test and receiver operating characteristic curve (ROC). RESULT: The success rate of pulpotomy was 88 % at 12-months. There was a significant difference between the median concentrations of aMMP-9 in pulpal blood of teeth with normal pulps (52 (12-96) ng mL-1 :) and SIP (193.3 (25.8-607.7) ng mL-1 :) (P = 0.0003) and successful (132.3 (25.8-548.3) ng mL-1 :) and failed cases (512.4 (334.8-607.7 ng mL-1 :) (P = 0.0015) of MTA pulpotomy. A significant association was established between aMMP-9 concentration and outcome of pulpotomy. The area under the receiver operating characteristics curve (0.9484, 95%CI) suggested excellent discriminatory power of aMMP-9 concentration in pulpal blood to predict the pulpotomy outcome. CONCLUSION: The pulpal blood concentration of aMMP-9 was significantly associated with the outcome of pulpotomy in teeth with symptomatic irreversible pulpitis, where it may be used as a potential prognostic biomarker.

Operating list composition and surgical performance.

BACKGROUND: Recent reviews suggest that the way in which surgeons prepare for a procedure (warm up) can affect performance. Operating lists present a natural experiment to explore this phenomenon. The aim was to use a routinely collected large data set on surgical procedures to understand the relationship between case list order and operative performance. METHOD: Theatre lists involving the 35 procedures performed most frequently by senior surgeons across 38 private hospitals in the UK over 26 months were examined. A linear mixed-effects model and matched analysis were used to estimate the impact of list order and the cost of switching between procedures on a list while controlling for key prognosticators. The influence of procedure method (open versus minimally invasive) and complexity was also explored. RESULTS: The linear mixed-effects model included 255 757 procedures, and the matched analysis 48 632 pairs of procedures. Repeating the same procedure in a list resulted in an overall time saving of 0·98 per cent for each increase in list position. Switching between procedures increased the duration by an average of 6·48 per cent. The overall reduction in operating time from completing the second procedure straight after the first was 6·18 per cent. This pattern of results was consistent across procedure method and complexity. CONCLUSION: There is a robust relationship between operating list composition and surgical performance (indexed by duration of operation). An evidence-based approach to structuring a theatre list could reduce the total operating time.

The Organization of Mitochondrial Supercomplexes is Modulated by Oxidative Stress In Vivo in Mouse Models of Mitochondrial Encephalopathy.

We examine the effect of oxidative stress on the stability of mitochondrial respiratory complexes and their association into supercomplexes (SCs) in the neuron-specific Rieske iron sulfur protein (RISP) and COX10 knockout (KO) mice. Previously we reported that these two models display different grades of oxidative stress in distinct brain regions. Using blue native gel electrophoresis, we observed a redistribution of the architecture of SCs in KO mice. Brain regions with moderate levels of oxidative stress (cingulate cortex of both COX10 and RISP KO and hippocampus of the RISP KO) showed a significant increase in the levels of high molecular weight (HMW) SCs. High levels of oxidative stress in the piriform cortex of the RISP KO negatively impacted the stability of CI, CIII and SCs. Treatment of the RISP KO with the mitochondrial targeted antioxidant mitoTEMPO preserved the stability of respiratory complexes and formation of SCs in the piriform cortex and increased the levels of glutathione peroxidase. These results suggest that mild to moderate levels of oxidative stress can modulate SCs into a more favorable architecture of HMW SCs to cope with rising levels of free radicals and cover the energetic needs.

Transrectal ultrasonography (TRUS)-guided pelvic plexus block to reduce pain during prostate biopsy: a randomised controlled trial.

OBJECTIVE: To assess the role of pelvic plexus block (PPB) in reducing pain during transrectal ultrasonography(TRUS)-guided prostate biopsy, compared with the conventional periprostatic nerve block (PNB). PATIENTS AND METHODS: A prospective, double-blind observational study was conducted with patients being randomised into three groups. Group-1 (47 patients) received intrarectal local anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group-2 (46 patients) received IRLA with periprostatic nerve block (PNB). Group-3 (46 patients) received only IRLA without any type of nerve block. The patients were requested to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two time points: VAS-1: during biopsy procedure and VAS-2: 30 min after the procedure. RESULTS: The mean age of the patients, mean volume of the prostates and mean serum PSA values were comparable among the three groups. The mean pain score during biopsy was significantly less in the PPB group [mean (range) sore of 2.91 (2-4)] compared with the PNB group [mean (range) score of 4 (3-5)], and both these groups were superior to the no nerve block group [mean score of 5.4 (3-7)]. There was no significant difference between the mean pain scores, 30 min after the procedure among the three groups with the mean (range) scores being 2.75 (2-4), 2.83 (2-4) and 2.85 (2-4), respectively. CONCLUSION: PPB is superior to conventional periprostatic nerve block (PNB) for pain control during TRUS-guided biopsy and both are in turn superior to no nerve block.

The Evolving Role of Artificial Intelligence in Radiotherapy Treatment Planning-A Literature Review.

This paper examines the integration of artificial intelligence (AI) in radiotherapy for cancer treatment. The importance of radiotherapy in cancer management and its time-intensive planning process make AI adoption appealing especially with the escalating demand for radiotherapy. This review highlights the efficacy of AI across medical domains, where it surpasses human capabilities in areas such as cardiology and dermatology. Focusing on radiotherapy, the paper details AI's applications in target segmentation, dose optimization, and outcome prediction. It discusses adaptive radiotherapy's benefits and AI's potential to enhance patient outcomes with much improved treatment accuracy. The paper explores ethical concerns, including data privacy and bias, stressing the need for robust guidelines. Educating healthcare professionals and patients about AI's role is crucial as it acknowledges potential job-role changes and concerns about patients' trust in the use of AI. Overall, the integration of AI in radiotherapy holds transformative potential in streamlining processes, improving outcomes, and reducing costs. AI's potential to reduce healthcare costs underscores its significance with impactful change globally. However, successful implementation hinges on addressing ethical and logistical challenges and fostering collaboration among healthcare professionals and patient population data sets for its optimal utilization. Rigorous education, collaborative efforts, and global data sharing will be the compass guiding its' success in radiotherapy and healthcare.

Identification of several small main-effect QTLs and a large number of epistatic QTLs for drought tolerance related traits in groundnut (Arachis hypogaea L.).

Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2n = 4x = 40), is a self pollinated and widely grown crop in the semi-arid regions of the world. Improvement of drought tolerance is an important area of research for groundnut breeding programmes. Therefore, for the identification of candidate QTLs for drought tolerance, a comprehensive and refined genetic map containing 191 SSR loci based on a single mapping population (TAG 24 x ICGV 86031), segregating for drought and surrogate traits was developed. Genotyping data and phenotyping data collected for more than ten drought related traits in 2-3 seasons were analyzed in detail for identification of main effect QTLs (M-QTLs) and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48-33.36% phenotypic variation explained (PVE) were identified using QTL Cartographer, while only 65 M-QTLs with 1.3-15.01% PVE were identified using QTLNetwork. A total of 53 M-QTLs were such which were identified using both programmes. On the other hand, GMM identified 186 (8.54-44.72% PVE) and 63 (7.11-21.13% PVE), three and two loci interactions, whereas only 8 E-QTL interactions with 1.7-8.34% PVE were identified through QTLNetwork. Interestingly a number of co-localized QTLs controlling 2-9 traits were also identified. The identification of few major, many minor M-QTLs and QTL × QTL interactions during the present study confirmed the complex and quantitative nature of drought tolerance in groundnut. This study suggests deployment of modern approaches like marker-assisted recurrent selection or genomic selection instead of marker-assisted backcrossing approach for breeding for drought tolerance in groundnut.

Sacral Insufficiency Fracture Following Pelvic Radiotherapy in Gynaecological Malignancies: Development of a Predictive Model.

AIMS: To investigate the time-to-event and the evolution of sacral insufficiency fractures in gynaecological patients receiving pelvic external beam radiotherapy (EBRT) in relation to dosimetric and imaging parameters across a spectrum of radiotherapy delivery techniques, and to develop a predictive model with a clinical nomogram to identify those at risk of sacral insufficiency fracture. MATERIALS AND METHODS: Patients who received radical or adjuvant pelvic EBRT for gynaecological malignancy between 2014 and 2019 were identified. The data collected were: demographics and clinical details; radiotherapy planning data: dose, fractionation, technique (fixed-field intensity-modulated radiotherapy, adaptive arc, and non-adaptive arc), 60 Gy simultaneous integrated boost. Each plan was examined to determine the sacral dose in 5%/Gy3 increments. Follow-up magnetic resonance scans were reviewed for insufficiency fractures, defined as linear low T1-weighted signal intensity with a high short-T1 inversion recovery (STIR) signal. The site of insufficiency fracture was recreated on the planning computed tomography, the dose to insufficiency fracture contours was recorded and insufficiency fractures were determined as healed with resolution of high STIR signal. Univariable analysis was conducted of the clinical variables. The area under the receiver operator characteristic curve and odds ratio of the risk prediction model with 95% confidence interval are reported with a nomogram for use in clinical practice. RESULTS: 115 patients were identified; the median imaging follow-up was 12 months (2-47). 37.4% developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. At the final radiological follow-up, 83.7% of insufficiency fractures remained active. The radiotherapy delivery technique was not associated with insufficiency fracture after adjusting for patient age (P = 0.115). The location of the 60 Gy simultaneous integrated boost planning target volume did not impact upon the site of insufficiency fracture or the dose received by the insufficiency fracture sites. Age and V40Gy3 are predictors for insufficiency fracture and form the clinical risk model (receiver operator characteristic 0.72). CONCLUSIONS: Age and V40Gy3 predict sacral insufficiency fractures; future work should focus on optimising radiotherapy planning with adoption of a bone-sparing planning approach for those patients at high risk of insufficiency fracture.

TGF ß-1 and WNT Signaling Pathways Collaboration Associated with Cochlear Implantation Trauma-Induced Fibrosis.

The crosstalk between TGF-ß1 and WNT pathways has been proven to regulate aspects of the development and tissue homeostasis processes. Recently, it has been demonstrated this collaboration also takes place during fibrotic diseases, where TGF-ß1 activates the WNT/ß-catenin pathway that results in dedifferentiation of fibroblasts into myofibroblasts, increased production of extracellular matrix components and fibrosis. Independent studies show the functions of these molecules during the development of the inner ears in several different species. However, little is known about the collaboration between TGF-ß1 and WNT in the injured inner ear and particularly how this collaboration affects the fibrotic process that often occurs following cochlear implantation. First, we used a cochlear explant model to study the effect of electrode insertion trauma and TGF-ß1 signaling in activation of the WNT pathway. Finally, adult TopGal mutant mice were used in vivo to track the activation of the WNT/ß-catenin in response to EIT. A chronic inflammatory response, increased cell proliferation and tissue remodeling are hallmarks of fibrotic disease. This study explores and highlights the collaboration between the TGF-ß1 and WNT pathways in the trauma-initiated fibrotic process within the implanted cochlea. WNT signaling is involved in the development of the inner ear and therefore a potential target in hair cell regeneration therapies. However, in light of our observations from the current study, manipulation of the WNT pathway by gene therapy techniques in the pathological ear seems a very complex process with an increased risk of inducing excessive fibrosis thereby compromising the efficacy of implant function. Anat Rec, 303:608-618, 2020. © 2019 American Association for Anatomy.

Provision of Organ at Risk Contouring Guidance in UK Radiotherapy Clinical Trials.

AIMS: Accurate delineation of organs at risk (OAR) is vital to the radiotherapy planning process. Inaccuracies in OAR delineation arising from imprecise anatomical definitions may affect plan optimisation and risk inappropriate dose delivery to normal tissues. The aim of this study was to review the provision of OAR contouring guidance in National Institute of Health Research Clinical Research Network (NIHR CRN) portfolio clinical trials. MATERIALS AND METHODS: The National Radiotherapy Quality Trials Assurance (RTTQA) Group carried out a two-round Delphi assessment to determine which OAR descriptions provided optimal guidance. RESULTS: Eighty-four clinical trials involving radiotherapy quality assurance were identified as either in recruitment or in setup within the NIHR CRN portfolio. Fifty-nine trials mandated OAR contouring. In total there were 412 OAR; 171 were uniquely named; 159 OAR had more than one name associated with a single structure, with the greatest nomenclature variation seen for the femoral head ± neck, the parotid gland, and bowel. The two-round Delphi assessment determined 42 OAR descriptions as providing optimal contouring guidance. CONCLUSIONS: This study identified the need for OAR nomenclature and contouring guidance consistency across clinical trials. In response to this study and in conjunction with the Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group, the RTTQA Group is in collaboration with international partners to provide consensus recommendations for OAR delineation in clinical trials.

Unexpected BP Sensitivity to Angiotensin II in a Patient With Coronavirus Disease 2019, ARDS, and Septic Shock.

We report the case of an 88-year-old man with coronavirus disease 2019 (COVID-19) who presented with ARDS and septic shock. The patient had exquisite BP sensitivity to low-dose angiotensin II (Ang-2), allowing for rapid liberation from high-dose vasopressors. We hypothesize that sensitivity to Ang-2 might be related to biological effect of severe acute respiratory syndrome coronavirus 2 infection. The case is suggestive of a potential role for synthetic Ang-2 for patients with COVID-19 and septic shock. Further studies are needed to confirm our observed clinical efficacy.

Laminin-coated electrodes improve cochlear implant function and post-insertion neuronal survival.

The benefits of Cochlear implant (CI) technology depend among other factors on the proximity of the electrode array to the spiral ganglion neurons. Laminin, a component of the extracellular matrix, regulates Schwann cell proliferation and survival as well as reorganization of actin fibers within their cytoskeleton, which is necessary for myelination of peripheral axons. In this study we explore the effectiveness of laminin-coated electrodes in promoting neuritic outgrowth from auditory neurons towards the electrode array and the ability to reduce acoustic and electric auditory brainstem response (i.e. aABR and eABR) thresholds. In vitro: Schwann cells and neurites are attracted towards laminin-coated surfaces with longer neuritic processes in laminin-coated dishes compared to uncoated dishes. In vivo: Animals implanted with laminin-coated electrodes experience significant decreases in eABR and aABR thresholds at selected frequencies compared to the results from the uncoated electrodes group. At 1 month post implantation there were a greater number of spiral ganglion neurons and neuritic processes projecting into the scala tympani of animals implanted with laminin-coated electrodes compared to animals with uncoated electrodes. These data suggest that Schwann cells are attracted towards laminin-coated electrodes and promote neuritic outgrowth/ guidance and promote the survival of spiral ganglion neurons following electrode insertion trauma.

Variation in age at ESRD in autosomal dominant polycystic kidney disease.

BACKGROUND: Heterogeneity manifest as more severe disease in successive generations has been attributed to genetic anticipation in patients with autosomal dominant polycystic kidney disease (ADPKD). We evaluated variation in age at end-stage renal disease (ESRD) in ADPKD families for evidence of anticipation. STUDY DESIGN: Retrospective. SETTING & PARTICIPANTS: 413 families with ADPKD seen at our single center between 1985 and 2004 (including 95 families with documented polycystic disease type 1 [PKD1] and 213 ADPKD families with parents born before 1930). PREDICTOR: Generational status. OUTCOME: Age at ESRD onset. MEASUREMENTS: Time to ESRD was evaluated by using survival analysis, Cox regression, and descriptive statistics. Unstable trinucleotide repeat expansion was evaluated by means of genotyping in 6 PKD1 families. RESULTS: We analyzed 413 ADPKD families (1,391 parent-offspring pairs) with known age at ESRD or last known age without ESRD (informative pairs). There was no difference in age at ESRD between parents and offspring by means of Cox regression after adjusting for correlations among family members and sex (hazard ratio, 1.019; 95% confidence interval, 0.919 to 1.13; P = 0.7). Similar analysis of PKD1 informative pairs and those with parents born before 1930 showed no differences in age at ESRD. Male ADPKD patients were 42% more likely to reach ESRD (P < 0.001), and male patients with documented PKD1 were 41% more likely to reach ESRD (P = 0.01) than female patients. LIMITATIONS: Hypertension treatment unknown. CONCLUSIONS: We found no evidence for anticipation of ESRD in patients with ADPKD; thus, the observed variation in age at ESRD may result from other genetic, sex, or environmental causes.

Array-based high-throughput DNA markers for crop improvement.

The last two decades have witnessed a remarkable activity in the development and use of molecular markers both in animal and plant systems. This activity started with low-throughput restriction fragment length polymorphisms and culminated in recent years with single nucleotide polymorphisms (SNPs), which are abundant and uniformly distributed. Although the latter became the markers of choice for many, their discovery needed previous sequence information. However, with the availability of microarrays, SNP platforms have been developed, which allow genotyping of thousands of markers in parallel. Besides SNPs, some other novel marker systems, including single feature polymorphisms, diversity array technology and restriction site-associated DNA markers, have also been developed, where array-based assays have been utilized to provide for the desired ultra-high throughput and low cost. These microarray-based markers are the markers of choice for the future and are already being used for construction of high-density maps, quantitative trait loci (QTL) mapping (including expression QTLs) and genetic diversity analysis with a limited expense in terms of time and money. In this study, we briefly describe the characteristics of these array-based marker systems and review the work that has already been done involving development and use of these markers, not only in simple eukaryotes like yeast, but also in a variety of seed plants with simple or complex genomes.

New frontiers for health information systems using Epi Info in developing countries: structured application framework for Epi Info (SAFE).

BACKGROUND: For more than two decades, Epi Info software has been used to meet the data management, analysis, and mapping needs of public health professionals in more than 181 countries and 13 languages. Until now, most Epi Info systems have been relatively simple, mainly because of a lack of detailed and structured guidance for developing complex systems. OBJECTIVE AND RESULTS: We created the structured application framework for Epi Info (SAFE), which is a set of guidelines that allows developers to create both simple and complex information systems using accepted good programming practices. This has resulted in application code blocks that are re-useable and easy to maintain, modify, and enhance. The flexibility of SAFE allows various aggregate and case-based application modules to be rapidly created, combined, and updated to create health information systems or sub-systems enabling continuous, incremental enhancement as national and local capacity increases. CONCLUSIONS: SAFE and Epi Info are both cost-free and have low system requirements--characteristics that render this framework and software beneficial for developing countries.

Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia

Aim: microRNA-423 is an oncogenic factor which is frequently upregulated in cancer. However, associations with breast cancer risk remain inconsistent. Therefore, we investigated the prevalence of microRNA-423 rs6505162C>T gene variation with breast cancer susceptibility in Saudi women. Methodology: This study was conducted on 100 breast cancer patients and 124 matched healthy individuals. Genotyping of the microRNA-423 rs6505162C/T gene variation was performed by using the amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution between the breast cancer cases and controls (p=0.0001), the frequencies of the genotypes CC,CT and TT being 25%, 52% and 23% in patients and 65%,20% and 15% respectively, in controls. The microRNA-423 C>T variant was associated with an increased risk of breast cancer in codominant models for (OR = 6.73, 95 % CI, 3.50-12.97; RR 2.35(1.67-3.30, p=0.0001) the microRNA-423TT genotype and (OR = 4.14, 95 % CI, 1.93-8.87; p=0.0003) microRNA-423CT (OR= 6.73, 95% CI, 3.50-12.97; p=0.0001) and also with the dominant model (OR 5.6(3.14-1.01), p=0.0001) CT+TT vs CC) with a non-significant association for the recessive model (OR=1.75, 95%CI=0.08-3.44, P=0.139, TT vs CC+CT). The T allele significantly increased the risk of breast cancer (OR =2.63, 95 % CI, 1.77-3.91; p=0.001) compared to the C allele. Some 6.73 ,4.14 and 2.63 fold increased risk of developing breast cancer was associated with TT and CT genotypes and the T allele of microRNA-423 in the northwestern region of Saudi Arabia. Conclusion: Our findings indicate that the microRNA-423 TT genotype and the T allele are associated with an increased susceptibility, metastasis and advanced stage of breast cancer in Saudi Arabian patients. Further studies with larger sample sizes are necessary to confirm our findings.

Wnt/ß-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression.

The chromatin organizer SATB1 has been implicated in the development and progression of multiple cancers including breast and colorectal cancers. However, the regulation and role of SATB1 in colorectal cancers is poorly understood. Here, we demonstrate that expression of SATB1 is induced upon hyperactivation of Wnt/ß-catenin signaling and repressed upon depletion of TCF7L2 (TCF4) and ß-catenin. Using several colorectal cancer cell line models and the APC min mutant zebrafish in vivo model, we established that SATB1 is a novel target of Wnt/ß-catenin signaling. We show that direct binding of TCF7L2/ß-catenin complex on Satb1 promoter is required for the regulation of SATB1. Moreover, SATB1 is sufficient to regulate the expression of ß-catenin, members of TCF family, multiple downstream effectors and mediators of Wnt pathway. SATB1 potentiates the cellular changes and expression of key cancer-associated genes in non-aggressive colorectal cells, promotes their aggressive phenotype and tumorigenesis in vivo. Conversely, depletion of SATB1 from aggressive cells reprograms the expression of cancer-associated genes, reverses their cancer phenotype and reduces the potential of these cells to develop tumors in vivo. We also show that SATB1 and ß-catenin bind to the promoters of TCF7L2 and the downstream targets of Wnt signaling and regulate their expression. Our findings suggest that SATB1 shares a feedback regulatory network with TCF7L2/ß-catenin signaling and is required for Wnt signaling-dependent regulation of ß-catenin. Collectively, these results provide unequivocal evidence to establish that SATB1 reprograms the expression of tumor growth- and metastasis-associated genes to promote tumorigenesis and functionally overlaps with Wnt signaling critical for colorectal cancer tumorigenesis.

Potential impact of (rs 4645878) BAX promoter -248G>A and (rs 1042522) TP53 72Arg>pro polymorphisms on epithelial ovarian cancer patients.

BACKGROUND: In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. OBJECTIVES: This study aimed at exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene-gene interaction of these two polymorphisms with risk of developing EOC. MATERIALS: The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. RESULTS: We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). CONCLUSIONS: The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.

Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients.

INTRODUCTION: TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients. MATERIAL AND METHOD: The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects. RESULTS: It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (χ (2) = 9.92, p = 0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95 % CI: 1.22-2.77), risk ratio 1.34 (95 % CI: 1.11-1.63), p value 0.003], HER2/neu status (p = 0.01) and distant metastasis (p = 0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04). CONCLUSION: Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53.