Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

Background: This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Materials and methods: Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. Results: The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. Conclusion: The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.

Nickel-Catalyzed Tandem Cyclization of 1,6-Diynes with Indolines/Indoles through Dual C-H Bond Activation.

A nickel-catalyzed site-selective tandem cyclization of 1,6-diynes with substituted indolines or indoles through consecutive dual C-H bond activation is described. In the reaction, substituted fused indole and carbazole derivatives were observed in good to excellent yields, in which three consecutive C-C bonds formed in one pot. Later, in the presence of DDQ, the aromatization of the indoline derivative was converted to the indole derivative. A possible reaction mechanism involving dual C-H bond activation as a key step was proposed to account for the present reaction.

Assessment of Treatment Plan Quality between Flattening Filter and Flattening Filter Free Photon Beam for Carcinoma of the Esophagus with IMRT Technique.

Background: As compared to the flattened photon beam, removing the flattening filter (FF) from the head of a gantry decreases the average energy of the photon beam and increases the dose rate, leading to an impact on the quality of treatment plans. Objective: This study aimed to compare the quality of intensity-modulated radiation therapy (IMRT) treatment plans for esophageal cancer with and without a flattened filter photon beam. Material and Methods: In this analytical study, 12 patients, who had already been treated with a 6X FF photon beam, were treated based on new IMRT methods using a 6X the flattening filter-free (FFF) photon beam. Both 6X FF IMRT and 6X FFF IMRT plans used identical beam parameters and planning objectives. All plans were evaluated with planning indices and doses for organs at risk (OARs). Results: Insignificant dose variation was for HI, CI, D98%, and V95% between FF and FFF photon beam IMRT plans. FF-based IMRT plan delivered a 15.51 % and 11.27% higher mean dose to both lungs and heart than the FFF plan, respectively. The integral dose (ID) for the heart and lungs was 11.21% and 15.51%, respectively, less in the IMRT plan with an FFF photon beam. Conclusion: In contrast to the FF photon beam, a filtered photon beam-oriented IMRT plan provides significant OAR sparing without losing the quality of the treatment plan. High monitor units (MUs), low ID, and Beam on Time (BOT) are major highlights of the IMRT plan with FFF beam.

XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population.

Background: Oral cancer is alarming disease in the developing countries like India. DNA repair capacity may affect by genetic polymorphisms in DNA repair genes and thus may cause to cancer. XRCC3 involves in homologous recombination repair pathway and repair DNA damage and crosslinks while, NBS1 participate in repair of double strand DNA break and starts the cell-cycle checkpoint signaling. Aims and Objectives: This study was to conducted to find the association of XRCC3, NBS1 polymorphisms with oral disease. Results: TT genotype of XRCC3 was associated with high risk of precancerous lesions and oral cancerous lesions (P value=0.0001, OR=9.68, 95% CI=2.82-33.21; and P value=0.0001, OR=13.10, 95% CI=3.38-50.73 respectively). We did not observe any interactions of XRCC3 polymorphism with demographic parameters in influencing the risk of oral diseases. Variant allele genotypes (CG, GG) of NBS1 (C>G) polymorphism showed protective association with Oral submucous fibrosis (OSMF), lichen planus as well as oral cancer (OR=0.31, OR=0.01; OR=0.39, OR=0.03; OR=0.43, OR=0.31 respectively). Particularly, tobacco chewer with CG & GG genotypes were at decrease risk of oral diseases (P value=0.02, OR=0.32, 95% CI=0.12-0.80). Compared to CC/CC combined genotype CG/CC, CG/CT, GG/CC and CG/CT genotypes decreased the risk of oral disease (OR=0.05, 0.47, 0.26 & 0.14 respectively). Conclusion: This study concludes that SNP in XRCC3, NBS1 affects susceptibility to oral disease.

The Taq 1 polymorphism of Vitamin D receptor gene is associated with oral cancer and preoral cancer in North Indian population.

Background: Oral cancer is known as one of the most common cancers, with a poor prognosis, related to delayed clinical diagnosis, either due to the lack of particular biomarkers related to the disease or costly therapeutic alternatives. Aims and Objectives: In this study association of single nucleotide polymorphism (Taq1, T>C) in Vitamin D receptor gene with oral cancer and pre oral cancer was studied. Materials and Methods: Total 230 patients of precancerous oral lesions (Leukoplakia 70, Oral Sub mucous fibrosis 90, Lichen Planus 70), 72 oral cancer patients and 300 healthy control subjects were genotyped by PCR-RFLP methods. Chi-square test was used for calculation of genotype and allele frequencies. Results: Mutant genotype CC as well as C allele were found to significantly decrease the risk of oral disease (P value=0.04, OR=0.60 and P value=0.02, OR=0.75 respectively). In particular, compared to non smokers, smokers with TC & CC genotypes were at decrease risk of oral diseases (P value=0.0001, OR=0.04). The mutant allele genotype CC as well as the mutant allele C showed protective association with leukoplakia (P value=0.01, OR=0.39 & P value=0.009, OR=0.59 respectively). However, individual with CC genotype had developed high cell differentiated grade at diagnosis (OR= 3.78, P value= 0.008). Conclusions: This study concludes that VDR (Taq1) polymorphism is associated with oral cancer and pre oral cancer susceptibility in North Indian population.

An Observational Study Depicting Role of p16 in Detecting Human Papilloma Virus in Oral and Oropharyngeal Cancer and Associated Factors.

The longstanding phrase, traditional risk factors like-smoking, tobacco and alcohol are the only causative agents of oral and oropharyngeal squamous cell carcinoma (SCC) is changing now. Etiological divergence is taking place which we have to know to reach upon an exact cause of the disease. Human papilloma virus (HPV) infection is a well-established cause of oral cancer. Escalating incidence of HPV associated cancer has a strong impact on its management. So, a concern clinician needs to get aware for it. Among various types of HPV, HPV-16 is more frequently associated with oral cancers. HPV detection will become a game changer in management of oral cancers. HPV infection and p16 protein expression has a strong and consistent correlation. Therefore, immunohistochemical analysis of p16 protein can be a surrogate biomarker in high risk groups. This hospital based prospective observational study recruited 180 subjects of oral and oropharyngeal SCC. We underwent immunohistochemical analysis of p16 in biopsy specimen of subjects and studied HPV status and associated environmental, clinical and behavioral factors. We observed 9.4% (17/180) incidence of p16 positivity with female predominance. Our observations showed that its prevalence was higher in urban patients who were non tobacco users, had sexually transmitted disease, early stage (T1-T2), poorly differentiated SCC with nodal metastasis. We conclude that keeping in mind HPV as a cause of oral and oropharyngeal SCC, p16 should be use as a biomarker for its detection in high risk cases.

Occupational lead exposure is an independent modulator of hypertension and poor pulmonary function: A cross-sectional comparative study in lead-acid battery recycling workers.

Blood lead level (BLL) is the primary biomarker for lead-exposure monitoring in occupationally exposed workers. We evaluated occupational lead-exposure (OE) impact on cardiopulmonary functions in lead-acid battery recycling unit workers. Seventy-six OE cases and 30 control subjects were enrolled for questionnaire-based socio-demographic, dietary, tobacco usage, and medical history data. Anthropometric measurements, systolic and diastolic blood pressure (SBP and DBP), and pulmonary function tests were performed. Venous blood was collected for BLL, hematological analysis, and biochemical analysis. OE caused a significant increase in BLL, SBP, DBP, and small airways obstruction in lung function tests. It also impaired platelet indices, affected renal and liver biochemical measurements, and promoted oxidative stress and DNA damage. Multilinear regression analysis suggested that BLL affected SBP (ß = 0.314, p = .034) and increased small airways obstruction (FEV1/FVC, ß = -0.37, p = .05; FEV25-75%, ß = -0.351, p = .016). Higher BLL appears to be an independent modulator of hypertension and poor pulmonary function upon occupational lead exposure in lead-acid battery recyclers.

Does Fluence Smoothing Reduce the Complexity of the Intensity-Modulated Radiation Therapy Treatment Plan? A Dosimetric Analysis.

Background: Intensity-modulated radiation therapy (IMRT) may have too many peaks and valleys, making the treatment plan undeliverable. When there are too many fluency differences between adjacent pixels in the X or Y directions, the X and Y smoothing factors are utilized as weighting factors to penalize this behavior. Generally, a high degree of complexity is accompanied by many monitor units (MUs), large number of segments, small sized segments, and complex segment shapes. The degree of plan delivery uncertainty can all increase with a higher detailed fluence map. Aim: This study aims to evaluate the dosimetric effects of various smoothing levels on the planning target volume (PTV) and organs at risk (OARs) for cervix cancer. Materials and Methods: IMRT treatment plans were re-optimized by combining several values of the X and Y penalty between 0 and 100. The dose-volume histogram assessed various dosimetric indicators for PTV and OARs. Additionally, gamma passing rates were evaluated and noted as an indicator of the complex treatment plan. Results: At X = 60, Y = 60 fluence map penalty, the conformity index (CI) value reached its highest value of 0.996 ± 0.004. At X = 0, Y = 0, the homogeneity index (HI) was determined to have a maximum value of 0.0628 ± 0.0235. The highest and lowest MU values were 2424.30 ± 471.12 and 1087.80 ± 91.57, respectively, with X = 0, Y = 0 and X = 100, Y = 100. At X = 100, Y = 100, the gamma passing rate reaches its highest value of 99.28% ± 0.44% and minimum value of 85.93% ± 3.87% at X = 0, Y = 0. Conclusion: The CI and HI values showed no discernible fluctuation, and the OAR doses were barely affected as smoothing was increased. When the smoothing factor was raised, the number of MUs sharply dropped, and a decrease in the number of segments and higher gamma passing rates were also seen.

The high-pressure bleb.

A 45-year-old male presented with a slowly progressive, painless swelling in his right eye for the past 6 months. He had undergone an open globe injury repair 10 years back and an eventful cataract surgery 5 years back. The presenting visual acuity in the affected eye was perception of light with inaccurate projection of rays. The intraocular pressure was 44 mm Hg with advanced glaucomatous cupping. The swelling was identified to be a communicating sub-tenon cyst secondary to scleral wound dehiscence from secondary angle closure glaucoma. Wound re-suturing, cyst excision and diode laser cyclophotocoagulation was performed in a single sitting, with explained poor visual prognosis.

Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources: 60Co and 192Ir.

BACKGROUND: Iridium-192 (192Ir) has been a widely accepted radioisotope for high-dose-rate (HDR) brachytherapy. Recently, Cobalt-60 (60Co) radioisotope with a longer half-life (5.26 years) has been gaining popularity due to economic and logistical reasons as compared with the traditional 192Ir. AIM: This study aimed to evaluate and compare the integral dose (ID) to the target and organs at risk (OARs) with two HDR brachytherapy sources in brachytherapy treatment of carcinoma uterine cervix to find appropriate HDR radioisotopes for clinical benefit. MATERIALS AND METHODS: This is a retrospective analysis of 52 computed tomography image-based brachytherapy plans of 52 patients who have received intracavitary treatment with 192Ir HDR source. For each patient plan, one additional set of plan was created using 60Co source in place of 192Ir source keeping the same dwell position, and again dose was optimized. The volume and mean dose for target, OARs, and volume structures of 400%, 200%, 150%, 100%, and 50% were recorded for the estimation and comparison of ID. RESULTS: The mean ID to high-risk clinical target volume was significantly higher by 5.84% in 60Co plan than that in 192Ir plan. For OARs, the mean ID to the rectum was significantly higher by 2.60% in 60Co plan as compared to 192Ir plan, whereas for bladder and sigmoid colon, it was lower in 60Co plan than that in 192Ir plan. The mean ID of central dose volume structures of 400%, 200%, 150%, 100%, and 50% was higher by 12.97%, 9.77%, 8.16%, 6.10%, and 3.22%, respectively, in 60Co plan than that of 192Ir plan. CONCLUSION: The results of our study concluded that 192Ir HDR radioisotope should be preferred for intracavitary brachytherapy due to its ideal physical characteristics for better clinical outcomes.

PARP-1 induces EMT in non-small cell lung carcinoma cells via modulating the transcription factors Smad4, p65 and ZEB1.

AIM: To study the role of PARP-1 in EMT of non-small cell lung carcinoma. MATERIALS AND METHODS: We used H1299 and H460 lung cancer cells for knockdown study of PARP-1 using shPARP-1 lentiviral particle. We performed western blotting, confocal microscopy, semi-quantitative PCR, wound healing and colony formation assays. BACKGROUND AND KEY FINDINGS: PARP-1 (poly-ADP ribose polymerase-1) is a multi-domain protein having DNA binding, auto-modification and catalytic domain, that participates in many biological processes including DNA damage detection and repair, transcription regulation, apoptosis, necrosis, cancer progression and metastasis. Metastasis is a leading cause of death in cancer patients, which starts in epithelial tumors via initiating epithelial to mesenchymal transition. There are various transcription factors involved in EMT including Snail-1, Smads, p65, ZEB1 and Twist1. We studied the effect of PARP-1 knockdown on EMT in non-small cell lung cancer cell line H1299. We found a significant increase in epithelial marker including ZO1 and ß-catenin, while prominent decrease in the mesenchymal marker vimentin after PARP-1 knockdown in H1299 cells. Transcription factors including p65, Smad4 and ZEB1 showed significant decrease with concurrent expression of EMT markers. Cell migration and colony formation decreased after PARP-1 knockdown in H1299 cells. SIGNIFICANCE: Overall, the shRNA mediated knockdown of PARP-1 in H1299 cells resulted in reversal of EMT or mesenchymal to epithelial transition (MET) characterized by an increase in epithelial markers and a decrease in mesenchymal markers, via down-regulating transcription factors including Smad4, p65 and ZEB1. Thus PARP-1 has a role in EMT in lung cancer.

Safety and efficacy of incisional goniotomy as an adjunct with phacoemulsification in primary angle-closure glaucoma.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of incisional goniotomy as an adjunct to phacoemulsification in primary angle-closure glaucoma (PACG) patients. METHODS: Consecutive patients with PACG (high or borderline IOP) deemed fit for phacoemulsification were enrolled. After phacoemulsification, incisional goniotomy was performed with or without goniosynechialysis. Patient demographic profile, clinical data, and adverse events, if any, were analyzed during at least a 6-month follow-up period. Success was defined as IOP of 18 mm Hg or lesser with or without medications. SETTING: Tertiary care Ophthalmic hospital. DESIGN: Prospective interventional case series. RESULTS: Of 46 eyes (38 patients) included, 69.6% eyes were classified as having advanced glaucoma. The mean treated IOP decreased by 7.3 ± 1.0 (SE) mm Hg (95% CI, 5.2-9.3) from 21.4 ± 6.6 to 14.2 ± 3.7 mm Hg at a mean duration of 11.7 ± 5.5 months (6-22 months) postoperatively (P < .001, paired t test). There was 66.6% reduction in median number of hypotensive medications (P < .001, Wilcoxon signed-rank test). Observed complications included hyphema (13 eyes [28%]), IOP spike (3 eyes [6.5%]), and cyclodialysis (1 eye [2.17%]). High treated IOP and number of medications were significantly associated with failure in univariate analysis (P < .05, Fisher exact test). The cumulative survival probability for qualified success at 22 months was 87.8% ± 0.07 (95% CI, 0.65-0.96). CONCLUSIONS: Incisional goniotomy as an adjunct with phacoemulsification resulted in a significant and sustained reduction in IOP along with decrease in number of glaucoma medications in chronic PACG eyes, irrespective of the disease stage.

Study 1: Evaluation of the signs of deficient posterior capsule in posterior polar cataracts using anterior segment optical coherence tomography.

PURPOSE: To systematically observe and analyze the signs of deficient posterior capsule in posterior polar cataracts. DESIGN: Ambispective observational study. PARTICIPANTS: Cases with posterior polar cataracts. METHODS: Eyes with diagnosed posterior polar cataracts were imaged on anterior segment optical coherence tomography (AS-OCT). A detailed assessment was performed to note the morphology of the posterior opacity, posterior capsule, and the common patterns to indicate their abnormality. In addition, generalized observation of the morphology was also performed about intraoperative surgical experiences. RESULTS: A total of 101 eyes were included. Mean patient age was 52.85 ± 10.72 years. The posterior capsule integrity was identified as intact in 91 eyes and abnormal/deficient in 10 eyes (9 had intraoperative defective capsule). These deficient/abnormal morphologies were classified into 3 categories: conical (n = 2), moth-eaten (n = 5), and (3) ectatic (n = 3). Similarly, depending on the presence of hypoechoic spaces between the opacity and the capsule, remaining posterior polar cataracts were categorized into 2 generalized morphological types: without hypoechoic areas (n = 40) and with hypoechoic areas (n = 51). In the without hypoechoic areas group, 6 cases developed capsular rent; in the with hypoechoic areas group, 1 case developed capsular rent. CONCLUSIONS: In posterior polar cataracts, the deficient/abnormal capsular morphology could be specifically categorized into 3 categories, conical, moth-eaten, and ectatic types. In addition, to predict the ease of intraoperative separation between the opacity and the capsule, generalized categorization might help in better case management.

Quantification of Iridotrabecular Contact in Primary Angle-Closure Disease.

PRECIS: Iridotrabecular contact (ITC), a measure of angle closure, can be quantified along with other angle parameters on anterior segment optical coherence tomography (ASOCT). Hence, angle changes and angle closure mechanisms can be detected predicting the efficacy of iridotomy. PURPOSE: To assess 360-degree ITC and ocular parameter changes, after laser peripheral iridotomy (LPI), in primary angle-closure disease (PACD) subgroups. METHODOLOGY: This was a prospective observational study including 90 subjects, 30 each of primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Anterior segment OCT parameters were measured before and 3 weeks after LPI ITC: central anterior chamber depth, lens vault, angle-opening distance, angle recess area, trabecular iris space area, trabecular iris angle at 500 and 750 µm from scleral spur. RESULTS: ITC was highest in PACG, 81.43%±22.39%, followed by PAC, 28.53%±21.30%, and PACS, 10.76%± 8.54% (P=0.011). There was a significant decrease in ITC in all 3 groups after iridotomy (P<0.001), with a residual ITC of 68.56%±26.44% in PACG, 18.23%±15.98% in PAC, and 5.13%±5.11% in PACS. A significant positive correlation was seen between the extent of ITC, baseline intraocular pressure, and visual field index. ITC was highest in eyes with exaggerated lens vault (77.3%±32.03%), as compared with eyes having a plateau iris configuration or relative pupillary block configuration (P<0.001). CONCLUSIONS: Iridotomy at any stage of PACD shows a significant decrease in ITC, with areas of residual ITC. Even in PACG, the iridotomy is effective in exposing parts of the trabecular meshwork that had contact earlier. Greater baseline ITC and postlaser ITC are a biomarker for higher intraocular pressure and greater visual field damage, which need lifelong review and appropriate management.

Clinical and ASOCT evaluations of 'bleb-sparing epithelial exchange' in paediatric and adult dysfunctional blebs over 5 years.

PURPOSE: To evaluate the long-term outcome of 'bleb-sparing epithelial exchange' surgery for dysfunctional filtering blebs in paediatric and adult eyes. METHODS: Patients who had undergone bleb revision ≥ 5 years back and were on regular follow-up were included. Age, ocular diagnosis, details of primary filtering surgery including mitomycin-C (MMC) usage, indication and year of bleb revision were recorded. After bleb revision, the mean intraocular pressure (IOP), glaucoma medications and best corrected visual acuity (BCVA) up to 5 years were noted. On last review, clinical details, bleb characteristics and swept source anterior segment tomographic (SSOCT) assessment of bleb were recorded. Comparative analysis of paediatric and adult eyes was performed. MAIN OUTCOME MEASURES: Change in IOP and BCVA. 'Complete success' was defined as IOP ≥ 6 to ≤ 18mmHg without use of any topical glaucoma medications and 'Qualified success' when ≥ 1 topical glaucoma medication(s) was required. RESULTS: A total of 51 eyes of 51 consecutive patients were studied, among which 22 were children. The mean duration between filtering surgery and bleb revision was 4.54 ± 1.53 years in paediatric and 6.48 ± 3.5 years in the adult group, p = 0.04. Children underwent trabeculotomy + trabeculectomy with 0.04% MMC, while adults underwent trabeculectomy with 0.02% MMC. The mean pre-revision IOP was 6.38 ± 2.80 and 6.51 ± 2.78 mmHg in the paediatric and adult group respectively, p = 0.86. At 3 months post-revision, it increased to 11.81 ± 3.48 and 12.75 ± 3.52 mmHg respectively (p < 0.001). At final review, mean IOP of paediatric group was 10.90 ± 2.59 and adult group was 11.86 ± 2.66 mmHg, p = 0.20. At 5 years, complete success was 68.18% and 72.41%, and qualified success was 31.87% and 27.59% in the former and latter group respectively, p = 0.49. No failures were seen. Kaplan-Meier probability at 5 years for IOP target ≤ 18, ≤ 15 and ≤ 12 in children was 95.45%, 63.64% and 50% and in adults 93.10%, 65.52% and 41.38% respectively. BCVA improved up to 1 year in paediatric group, with continued improvement in adults up to 3 years. SSOCT measured bleb height was 0.88 ± 0.37 and 1.32 ± 0.49mm in children versus adults (p = 0.006) and wall thickness, 0.35 ± 0.22 and 0.58 ± 0.24mm respectively, p = 0.008. CONCLUSION: Bleb-sparing epithelial exchange is an equally safe and effective technique with good long-term success in both paediatric and adult dysfunctional blebs.

Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population.

Background: Environmental carcinogens cause DNA damages which if not repaired properly, may increase the risk of cancer. The Xerodermapigmentosum group D (XPD) and group G (XPG) genes are essential genes for DNA repair and alteration in DNA repair causes cancer. The present study aimed to evaluate the relationship between XPD and XPG polymorphisms and risk of oral pre cancer and cancer. Methods: Present study genotyped 302 samples of oral diseases and 300 controls for XPD (A/C) and XPG (G/C) polymorphisms with PCR-RFLP method. Results: Our result showed that compared to AA genotype frequency of AC and CC genotype for XPD(A/C) polymorphism were significantly lower among cases than in control and are associated with decreased risk of oral diseases (OR= 0.621 and 0.603 respectively). In contrast with reference to GG genotype the frequency of CC genotype of XPG (G/C) was significantly higher in case than in control population (p value=0.004) and found to increase the risk of oral diseases (OR= 2.077). Particularly C allele for XPD A/C polymorphism was found to be associated with decreased risk of Lichen planus and increased risk of ( OR = 0.470 and 1.541 respectively) oral cancer. While C allele of XPG G/C polymorphism significantly increased the risk of Oral Submucous Fibrosis and Leukoplakia (OR= 1.879 and 1.837 respectively) but not of Lichen planus and oral cancer. In combined genotype analysis from the aforesaid polymorphisms presence of C allele for XPD (A/C) polymorphisms were found to decrease the risk of oral diseases. However, the same C allele was observed to increase the chance of having high stage disease (OR= 5.71) with nodal involvement (OR= 6.78) once the cancer been initiated. Conclusion: This work shows association of XPD (A/C), XPG (G/C) polymorphisms with the development of pre oral cancer as well as oral cancer and its clinical courses.

KLF4 sensitizes the colon cancer cell HCT-15 to cisplatin by altering the expression of HMGB1 and hTERT.

AIMS: Insensitivity of cancer cells to therapeutic drugs is the most daunting challenge in cancer treatment. The mechanism of developing chemo-resistance is only partly understood to date. In continuation of some earlier reports, we hypothesize that KLF4, a key transcription factors that also has a crucial role in maintaining the stemness in cancer cells, may offer a basis for chemo-resistance. MAIN METHODS: Sensitivity of cells to cisplatin was analyzed by cell proliferation, colony formation, and cell growth assay. Cell cycle analysis and immunophenotyping were used to measure cell cycle arrest and level of reactive oxygen species respectively. Immunoblotting was used to analyze the change in expression hTERT and HMGB1 involved in KLF4 mediated cisplatin resistance. KEY FINDINGS: We found that KLF4 expression sensitizes cancer cell to cisplatin cytotoxicity. Further, KLF4 promotes the cisplatin-mediated G2/M cell cycle arrest while KLF4 knocked down induces cisplatin-mediated S-phase arrest compared to control. Decreased level of reactive oxygen species (ROS) in cisplatin-treated and KLF4 knocked down HCT-15 cells compared to vector control, accounting for increased cell survival. Immuno-blotting showed that KLF4 positively regulates expression of the survival proteins hTERT and HMGB1 while in presence of cisplatin, expression of HMGB1 and hTERT is negatively regulated by KLF4. SIGNIFICANCE: This study suggests the involvement of KLF4-HMGB1/hTERT signaling in offering the basis for chemo-resistance in colon cancer cells and KLF4 overexpression as a probable strategy for sensitizing drug-resistant cancer cells to chemotherapy. The present study opens up new avenues for cancer research and therapeutics.

Changes in Intraocular Pressure and Angle Status After Phacoemulsification in Primary Angle Closure Hypertension.

PURPOSE: To study the change in intraocular pressure (IOP) and angle status after phacoemulsification in a cohort of primary angle closure hypertension (PACHT) patients. SETTING: Tertiary Eye Care, India. DESIGN: Prospective interventional case-series. METHODS: Case-series of 18 eyes of 18 patients. Preoperative biometry including axial length, anterior chamber depth (ACD), lens thickness, and central corneal thickness were studied. Preoperative and postoperative IOP, number of topical glaucoma medications, angle swept source optical coherence tomography (SS-OCT) parameters of nasal and temporal angle opening distance, trabecular iris space area, scleral spur angle, lens vault and circumferential iridotrabecular contact (ITC) were studied and their correlations derived. RESULTS: The mean preoperative IOP, 31±6 mm Hg, decreased to 14±1 mm Hg at 6-months postoperative period, P<0.001, a fall by 58±14%. The number of glaucoma medications reduced from 4(3-5) to 2(1-3), P<0.001. All SS-OCT studied parameters denoted significant angle widening postsurgery. The ITC% reduced from 52(16-100) to 19(0-97), P<0.001. The preoperative ITC showed moderate to strong correlation with all preoperative nasal and temporal angle parameters. It also showed moderate positive correlation with percentage fall in IOP at 1-month postoperative period. The preoperative ACD showed significant negative correlation with preoperative and postoperative ITC. CONCLUSIONS: PACHT patients benefit significantly from cataract surgery with marked angle widening, IOP reduction and a decrease in the number of glaucoma medications. The SS-OCT derived circumferential iridotrabecular contact index can be used as the single best parameter to indicate the preoperative angle status and predict postoperative change in IOP, as against the numerous single section measured angle parameters.

Interfraction physical dose variations in high-dose-rate brachytherapy for carcinoma cervix based on computed tomography image dataset to find the compatibility of the first fraction plan to treat successive fractions.

CONTEXT: Due to limited resources and/or affordability by majority of the patients, many centers in low- and middle-income countries are still not able to adapt three-dimensional image-based brachytherapy planning in their routine practice. AIM: The aim of the study was to see the feasibility of using computed tomography (CT)-based plan of the first fraction to treat successive fractions of intracavitary brachytherapy based on the estimation of the physical dosimetric differences between successive applications. MATERIALS AND METHODS: CT image-based brachytherapy plans of 38 patients who received three insertions of intracavitary application with high-dose-rate brachytherapy have been analyzed. Revised plans for the second and third insertions were generated by adapting dwell time and dwell position of the first insertion plan. The dose to point "A" and maximum doses to 2, 1, and 0.1 cc volumes of the rectum and bladder have been used for dosimetric comparison. RESULTS: The statistical differences of mean point "A" doses were observed insignificant except between original and revised plans for the second insertions. The dosimetric differences between consecutive original and revised plans for the bladder and rectum have not shown any significance except minimum dose to 0.1 cc volume of the rectum for the third insertions. CONCLUSIONS: Dosimetric deviation for tumor and organs at risk is within acceptable limit while using CT image-based brachytherapy plan of the first fraction for treating successive fractions.

The Nuclear Translocation of Mitogen-Activated Protein Kinases: Molecular Mechanisms and Use as Novel Therapeutic Target.

The mitogen-activated protein kinase (MAPK) cascades are central signaling pathways that play a central role in the regulation of most stimulated cellular processes including proliferation, differentiation, stress response and apoptosis. Currently 4 such cascades are known, each termed by its downstream MAPK components: the extracellular signal-regulated kinase 1/2 (ERK1/2), cJun-N-terminal kinase (JNK), p38 and ERK5. One of the hallmarks of these cascades is the stimulated nuclear translocation of their MAPK components using distinct mechanisms. ERK1/2 are shuttled into the nucleus by importin7, JNK and p38 by a dimer of importin3 with either importin9 or importin7, and ERK5 by importin-α/ß. Dysregulation of these cascades often results in diseases, including cancer and inflammation, as well as developmental and neurological disorders. Much effort has been invested over the years in developing inhibitors to the MAPK cascades to combat these diseases. Although some inhibitors are already in clinical use or clinical trials, their effects are hampered by development of resistance or adverse side-effects. Recently, our group developed 2 myristoylated peptides: EPE peptide, which inhibits the interaction of ERK1/2 with importin7, and PERY peptide, which prevents JNK/p38 interaction with either importin7 or importin9. These peptides block the nuclear translocation of their corresponding kinases, resulting in prevention of several cancers, while the PERY peptide also inhibits inflammation-induced diseases. These peptides provide a proof of concept for the use of the nuclear translocation of MAPKs as therapeutic targets for cancer and/or inflammation.