Search

Background Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT). Purpose We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT. Methods We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues. Results First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction. Conclusion Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.

To elucidate the molecular processes associated with the development of myopic macular degeneration (MMD), we measured the intraocular concentrations of molecular factors in emmetropic and myopic eyes. This is a retrospective clinic-based case-control study that included eyes undergoing routine cataract surgery whereby aqueous humour samples were obtained. We measured the concentrations of pigment epithelium derived factor(PEDF), matrix metalloproteinase 2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-2), vascular endothelial growth factor isoform A(VEGF-A), interleukin 8(IL-8), interleukin 6(IL-6), C-reactive protein(CRP), angiopoietin 2(Ang2), and amphiregulin. 38 eyes (axial length (AL): 22.4–32.4 mm), including 12 highly myopic (HM) eyes (AL ≥ 26.5 mm) without MMD and 12 HM eyes with MMD but without neovascularization were included. Eyes with MMD were found to have significantly lower VEGF-A levels (p = 0.007) and higher MMP-2 levels (p = 0.02) than control eyes after adjusting for age and gender. MMP-2 levels correlated positively (r = 0.58, p = 0.002), while VEGF-A levels correlated negatively with longer axial length (r = −0.75, p P = 0.25) and MMP-2 (P = 0.69) were not significantly associated with MMD after adjusting for AL. These findings suggest that the predominant mechanism underlying the development of non-neovascular MMD may be axial elongation, driven in part by MMP-2 related mechanisms.

A yurveda has described many a psychiatric disorders in different contexts. Unma da is an entity where there is derangement of mind, cognition, orientation, memory, desire, habits, actions and rituals , ei ther individually or as a whole. All of the above faculties are not impaired in a single clinical entity. Obsessive compulsi ve disorder (OCD ) can be considered due to deviation of the mental attributes like cognition, will power, memory etc. which affects the day to day life of an individual. Management of psychiatric disorders in Ayurveda includes spiritual therapy, psychotherapy and pharmacotherapy focusing on the balancing of bodily and mental humors. Here in the case of OCD, vaata is the main humor viti ated among the three basic humors and the management should be directed to pacify all the three humors , with special consideration to vaata. Snehapaana is the important one among them. In the case of thought abnormalities, mental functions will be fogged u p . To cleanse the channel s, the dru g of choice should be pungent and having the property of srotosodhana i . e . clearing the channels . The selected drug in this study, Pancagavya ghri ta is an ideal drug in that sense. The ai m of this study wa s to assess the efficacy of Panc agavya ghrita in OCD when compared with t he supportive psychotherapy . The method of this study is randomized controlled trial with sample size 20 ; assessments were done according to Yale Brown Obsessive Compulsiv e Sc ale . T here were signific ant change s in the trial group and the control group . But there was no statistical significance on comparison between the two groups.

12056Background: Combinatorial immune checkpoint blockade (ICB) with radiotherapy (RT) potentiates anti-tumour response via modulation of the immune microenvironment. However, detailed host-specifi...

Aims: Emerging evidence in viral-associated oro- and naso-pharynx cancers supports the concept of radiotherapy (RT) dose de-intensification in these radiosensitive tumours. This notion is particularly relevant in the background that a majority of head and neck cancer patients develop severe late toxicities despite modern precision RT. A reasonable strategy could thus entail stratifying patients at risk of late toxicities to dose de-intensification. Here, we investigated the utility of a lymphocyte apoptosis (RILA) assay to predict for late toxicities in EBV-positive nasopharynx cancer patients. We also test if a multi-modal approach incorporating DNA damage induction and repair improves the prediction of clinical radiosensitivity. Methods: Assays were assessed retrospectively among survivors of a randomised controlled trial (NCC-0902), where patients were assigned to weekly cisplatin-RT with or without neoadjuvant gemcitabine, carboplatin, and paclitaxel. Late toxicities were assessed by CTCAE v.2 at the following intervals - 2-mo year 1, 4-mo year 2, 6-mo years 3-5, and annually thereafter; and considered severe if CTCAE v.2 ≥Grade 2. RILA was based on a fluorogenic inhibitor of caspases assay (48 h post-8 Gy). DNA damage induction and repair were assessed by semi-automated scoring of ϒH2AX foci at 30 min post-1 Gy and 24 h post-4 Gy, respectively. Results: Median follow-up of patients was 5.7 (range 4.6-7.4) years. Clinical and treatment indices, including assigned study arm and RT dosimetry to normal tissue structures, were balanced between patients with and without late toxicities (p >0.05). We observed a trend between decreasing RILA scores and increased risks of late toxicities; odds ratio (OR) 1.27 (95% CI = 0.92-1.72) for lowest quartile cut-off, corresponding to an AUC of 0.608 for prediction accuracy (p = 0.049). A multi-modal approach incorporating DNA damage induction and repair did not improve upon the predictive accuracy of RILA for clinical radiosensitivity. Independently, DNA damage induction and repair were not associated with risks of late toxicities; OR 1.03 (95% CI = 0.69-1.53, p = 0.901) and 1.04 (95% CI = 0.73-1.49, p = 0.829), respectively. Interestingly, onset of late toxicities was correlated to an improved disease-free survival in our cohort (5-y DFS = 94.1% vs 73.3%, no late toxicity, p = 0.003), which suggests a common mechanism underlying tumour and normal tissue radiosensitivity in EBV-positive nasopharynx cancer. Conclusions: Herein, we report on the potential utility of a RILA assay in stratifying for patients at risk of late RT-induced toxicities. The clinical implication of this assay is further exemplified by the observation of a superior survival in these sensitive individuals, which supports the approach of selecting this subgroup for treatment de-intensification. Citation Format: Kevin L.M. Chua, Shihabuddeen Waseem Ahamed, Ma Than Than Shwe, Li-lian Kwok, Joseph T.S. Wee, Terence W.K. Tan, Prakash M. Hande, Kai Rothkamm, Melvin L.K. Chua. Lymphocyte apoptosis as a predictive biomarker for radiotherapy de-intensification in EBV-associated nasopharynx cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1794. doi:10.1158/1538-7445.AM2017-1794

e17545 Background: Emerging evidence in viral-associated head and neck cancers supports the concept of dose de-intensification in these radiosensitive tumors, but different strategies exist in selecting patients for treatment de-intensification. We hypothesize that patients who develop severe late toxicities (LT) to radiation (RT) have better tumor control, due to a common radiosensitivity index. Here, we investigate the utility of a normal tissue radiosensitivity assay (RT-induced lymphocyte apoptosis, RILA) in predicting clinical outcomes (tumor control and normal tissue toxicity) of patients with EBV-associated nasopharynx cancer (NPC). Methods: RILA assay was assessed in a cohort of locally advanced NPC patients from a randomized controlled phase III trial (N = 172, NCC0901) of cisplatin-RT with or without induction gemcitabine, carboplatin and paclitaxel. LT was assessed by CTCAE v.2 at the following intervals (2 mo yr 1, 4 mo yr 2, 6 mo yr 3-5, annually thereafter). We performed the RILA assay (48 h post 8 Gy) in a subset of cases (N = 87). Results: At a median follow-up of 5.7y, DFS (3y 74.9% GCP vs 67.4% Control, p = 0.362) and incidence of severe Grade ≥3 LT did not differ between the treatment arms. In keeping with our hypothesis, onset of severe LT was associated with reduced risk of disease relapse; OR 0.19 (95% CI = 0.02 – 1.59, p = 0.168). High %RILA, stratified by top quartile, was associated with severe LT (OR 1.92 [95% CI = 0.67-5.5], p = 0.26); and lower rate of recurrence (4.5% (1/22), high %RILA vs19.7% (12/61), low %RILA, p = 0.086). Interestingly, subset analyses revealed that CD8+, but not CD4+ subpopulation of immune cells, was strongly associated with recurrence; OR 8.58 for low %CD8-RILA (p = 0.001). Conclusions: Herein, we showed that %RILA may be a useful biomarker for tumor and normal tissue radiosensitivity of EBV-associated NPC. If validated, this predictive assay will enable precision matching of RT-sensitive patients for de-intensification in EBV- and other viral-associated head and neck cancers. The association between tumor control and CD8-subset of immune cells suggests an immune dependency for RT.

Social disability has been found to be a potent predictor of symptom exacerbations and re­hospitalizations. It is clear that social skills training is an effective strategy. Accessibility for the mental health consumers and the availability of services are the two main reasons which highlights the felt need of the brief skill development program in the GHPU during their hospitalization. This article reviews the need for brief skills training to enhance client's social competence to reach optimal functioning which in turn may decrease the risk of relapse or revolving door syndrome and may prevent further deterioration of individual's skills during their long stay in a GHPU's.

In the title polymeric complex, [Co(NCS)2{SC(NH2)2}2]n, the asymmetric unit comprises a CoIIion, which is situated on an inversion centre, anN-bound thiocyanate anion and a μ2-bridging thiourea molecule. The CoIIatom is coordinated in a distorted octahedral fashion within an N2S4donor set. The bridging thiourea ligands link CoIIions into a polymeric chain extending along [100]. The molecular conformation is stabilized by intramolecular N—H...N hydrogen bonds, which generateS(6) ring motifs. The crystal packing is stabilized by N—H...S interactions, which connect the chains into a three-dimensional architecture.

Single crystal of bis mercury ferric chloride tetra thiocyanate [Hg 2 FeCl 3 (SCN) 4 ; (MFCTC)] was grown from ethanol–water (3:1) mixed solvent using slow evaporation solvent technique (SEST) for the first time. The cell parameters of the grown crystal were confirmed by single crystal XRD. The coordination of transition metal ions with the SCN ligand is well-identified using FT-IR spectral analysis. The chemical composition of MFCTC was confirmed using CHNS elemental test. The ESR spectral profile of MFCTC was recorded from 298 K to 110 K, which strongly suggests the incorporation of Fe 3+ ion and its environment with respect to SCN ligand. The HPLC chromatogram of MFCTC highlights the purity of the compound. The UV–Vis–NIR studies revealed the ultra violet cut-off wavelength of MFCTC in ethanol as 338 nm. The dielectric constant and dielectric loss of the sample were studied as a function of frequency and temperature. The TGA–DTA and DSC thermal analysis show that the sample is thermally stable up to 234.31 °C, which is comparatively far better than the thermal stability of Hg 3 CdCl 2 (SCN) 6 ; (171.3 °C) and other metal–organic coordination complex crystals such as CdHg(SCN) 4 (198.5 °C), Hg(N 2 H 4 CS) 4 Mn(SCN) 4 (199.06 °C) and Hg(N 2 H 4 CS) 4 Zn(SCN) 4 (185 °C). The SHG conversion efficiency of MFCTC is found to be higher than KDP.

Single crystals of mercury cadmium chloride thiocyanate [Hg3CdCl2(SCN)6; (MCCTC)] were grown from ethanol solvent using slow solvent evaporation technique for the first time. The cell parameters of the grown crystals of MCCTC were confirmed by single crystal X-ray diffraction technique. The various functional groups of resulting compound were well-identified using FT-IR analysis. The UV-Vis-NIR studies revealed that the ultra violet cut off wavelength lies at 270 nm. It is also interesting to note that the sample exhibited wide range of optical transparency from 270 to 2000 nm in ethanol solution, which might be due to the incorporation of the halogen ion (Cl-) in the grown crystal of MCCTC. The second harmonic generation efficiency of MCCTC is found to be superior (about seventeen times) to KDP and (about three times) urea. TGA-DTA and DSC analysis showed that the thermal stability of the sample is retained up to 171.3°C above which phase change occurred from HgCdCl2(SCN)6 to CdHg(SCN)4 with other fragme...

Combining the optical transparency together with greater nonlinearity and thermal stability is a challenge to people who have thirst to design new category NLO materials. In the present work, an optically transparent prism shaped Urea-L-tartaric acid (ULTA) single crystals were grown using simple slow evaporation technique. The cell parameters of the grown crystals were determined by SXRD. The crystalline samples of ULTA were subjected to UV-Vis-NIR and thermal analysis. The optical studies established the transparency range of the ULTA crystal from 250 nm to 2000 nm except a predominant peak observed at 1989 nm. The melting point of the sample is found to be 209.38 °C, which is far greater than Urea (132°C), UDTA (96.3°C). The refractive index calculation was also made and reported.

Disability in the area of psychosocial role functioning is found to be present even while getting discharged from the hospitals or GHPU's; since the current scenario in India focus primarily on pharmacological/somatic treatment with less emphasis on structured psychosocial therapies/interventions during hospitalization. This poses a challenge for the care givers and burdens them with additional duties of assisting the unproductive family member after discharge. This in turn creates misconception about the progress of the client or the expectation of treatment efficacy. The importance of structured psychosocial interventions during the hospitalization in a GHPU has been discussed elsewhere, however, the premises/existing settings pause as a challenge to introduce such programs even with the awareness of the benefits. It's also noticed that in India, majority of consumers prefer to avail treatment from GHPU than any alternative patters of care. Also, the related publications reveal the availability and the benefits of daycare center attached to a GHPU. This highlights the felt-need of having a daycare center attached to every GHPU in India for improving mental healthcare system of the country.