Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial.

BACKGROUND: In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression. PATIENTS AND METHODS: Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint. RESULTS: At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings. CONCLUSIONS: CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC.

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.

BACKGROUND: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival. PATIENTS AND METHODS: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed. RESULTS: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population. CONCLUSION: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer.

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

The burden of COVID-19 infection in a rural Tamil Nadu community.

BACKGROUND: There have been over 30 million cases of COVID-19 in India and over 430,000 deaths. Transmission rates vary from region to region, and are influenced by many factors including population susceptibility, travel and uptake of preventive measures. To date there have been relatively few studies examining the impact of the pandemic in lower income, rural regions of India. We report on a study examining COVID-19 burden in a rural community in Tamil Nadu. METHODS: The study was undertaken in a population of approximately 130,000 people, served by the Rural Unit of Health and Social Affairs (RUHSA), a community health center of CMC, Vellore. We established and evaluated a COVID-19 PCR-testing programme for symptomatic patients-testing was offered to 350 individuals, and household members of test-positive cases were offered antibody testing. We also undertook two COVID-19 seroprevalence surveys in the same community, amongst 701 randomly-selected individuals. RESULTS: There were 182 positive tests in the symptomatic population (52.0%). Factors associated with test-positivity were older age, male gender, higher socioeconomic status (SES, as determined by occupation, education and housing), a history of diabetes, contact with a confirmed/suspected case and attending a gathering (such as a religious ceremony, festival or extended family gathering). Amongst test-positive cases, 3 (1.6%) died and 16 (8.8%) suffered a severe illness. Amongst 129 household contacts 40 (31.0%) tested positive. The two seroprevalence surveys showed positivity rates of 2.2% (July/Aug 2020) and 22.0% (Nov 2020). 40 tested positive (31.0%, 95% CI: 23.02 - 38.98). Our estimated infection-to-case ratio was 31.7. CONCLUSIONS: A simple approach using community health workers and a community-based testing clinic can readily identify significant numbers of COVID-19 infections in Indian rural population. There appear, however, to be low rates of death and severe illness, although vulnerable groups may be under-represented in our sample. It's vital these lower income, rural populations aren't overlooked in ongoing pandemic monitoring and vaccine roll-out in India.

Molecular structure analysis and biological properties investigation on antiseptic drug; 2-amino-1-phenyl-1-propanol using spectroscopic and computational research analysis.

The inducement of physical, chemical, structural and biological properties to entice of pharmaceutical property was analyzed by Vibrational spectroscopic, biological and theoretical tools. The structural arrangement for describing structure activity was investigated by injecting ligand groups in internal coordinate system by molecular tools (FT adopted IR, Raman, and NMR). Bond length and bond angle strain was pronounced much due to the chemical equivalent forces extension due to the injection of substitutional groups on base compound and thus non-Centro symmetry was processed. The molecular charge depletion profile was thoroughly studied to persuade protonic and electronic delocalization setup for arranging the drug potential. The chemi-equivalent potential exchange was monitored among different parts of the molecule for obtaining drug mechanism. The biological profile was keenly observed to look at the biological ambiance of the present molecule to fabricate advanced drug. The Lipinski five rule parameters; MV = 137.18, LogP = 0.27, HBD = 2, HBA = 2 and TPSA = 46.2 A2 showed the enhancement of additive drug quality. The exchange of oscillating chemical energy in the core and allied carbons of the base skeleton was keenly noted to find the prearranged chemical environment for successful drug mechanism. The non bonded transitions between Lewis acid and base of bonded molecular system were observed to determine the restoring potential to customize drug potential. The drug assistance for enantiomer characteristics of chirality sequence was displayed to expose the toxicity effect of the molecule. The active molecular bondings on different sites of molecule were measured by estimating polarizability and associated biological inhibition was validated.

Synthesis opto-electronic characterization and NLO evaluation of 6-methyl 5-nitro Uracil crystal using XRD, spectroscopic and theoretical tools.

The organic composite crystal for 6-methyl 5-nitro Uracil was grown using slow-evaporation method and the crystal quality was checked by observing the peaks in XRD pattern. The molecular structure of 6-methyl 5-nitro Uracil was used to find crystal parameters for determining NLO activity. The appropriate electronic geometrical structure was keenly noted and the transitional energy exchange was studied and thereby fine-tuning of crystal performance was made by adopting suitable electron-accepting and with-drawing substitutional groups. The crystal parameters; a≠b≠c confirmed the orthorhombic lattice pattern. The space group was found as P21/a and Transparency range was observed as 409-1256 nm. The laser measurements were made and laser Damage threshold was estimated at 10 ns[1.08-3 GW/cm2]. The scattering characteristics of bond networks over the molecule were observed by studying vibrational characteristics of elemental bonds. The hybrid calculations on DFT methods were made using B3LYP/6-311++(D,P) basis set. The chemical shift was observed and retracing chemical potential was identified from the parametric oscillation. The frontier molecular interactions between ground and excited orbital lobe overlapping segments were noted and type of interaction system was identified. The electronic and protonic transfer energy was measured and the origination point of equivalent chemical potential was acknowledged. The NBMO profile was keenly grafted and the transitional energy was measured at every consumed electronic energy band. The vibrational circular dichroic image for all vibrational regions was sketched and the rate of transmission and absorption ratio was verified from peak intensity.

Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis.

BACKGROUND: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. PATIENTS AND METHODS: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum-pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. RESULTS: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum-pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum-pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinum-pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18-1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16-0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum-pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum-pemetrexed arm. CONCLUSIONS: In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum-pemetrexed, which possibly reflects the high crossover rate of patients from platinum-pemetrexed to osimertinib. CLINICAL TRIALS NUMBER: ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.

Molecular mechanisms in grass-Epichloë interactions: towards endophyte driven farming to improve plant fitness and immunity.

All plants harbor many microbial species including bacteria and fungi in their tissues. The interactions between the plant and these microbes could be symbiotic, mutualistic, parasitic or commensalistic. Mutualistic microorganisms are endophytic in nature and are known to play a role in plant growth, development and fitness. Endophytes display complex diversity depending upon the agro-climatic conditions and this diversity could be exploited for crop improvement and sustainable agriculture. Plant-endophyte partnerships are highly specific, several genetic and molecular cascades play a key role in colonization of endophytes in host plants leading to rapid changes in host and endophyte metabolism. This results in the accumulation of secondary metabolites, which play an important role in plant defense against biotic and abiotic stress conditions. Alkaloids are one of the important class of metabolites produced by Epichloë genus and other related classes of endophytes and confer protection against insect and mammalian herbivory. In this context, this review discusses the evolutionary aspects of the Epichloë genus along with key molecular mechanisms determining the lifestyle of Epichloë endophytes in host system. Novel hypothesis is proposed to outline the initial cellular signaling events during colonization of Epichloë in cool season grasses. Complex clustering of alkaloid biosynthetic genes and molecular mechanisms involved in the production of alkaloids have been elaborated in detail. The natural defense and advantages of the endophyte derived metabolites have also been extensively discussed. Finally, this review highlights the importance of endophyte-arbitrated plant immunity to develop novel approaches for eco-friendly agriculture.

Un-riped fruit pods of Prosopis cineraria (L.) Druce ameliorates Cisplatin therapy-induced partial testicular atrophy in male Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Prosopis cineraria (L.) Druce is a plant that is widely found in dry parts of India. The unripe fruit pod has a very specific traditional claim of treating male infertility and increasing sperm volume and count. AIM: The present work was endeavored to investigate the long-standing traditional claim of P. cineraria on meliorating male fertility. The study focussed on cancer therapy-induced male infertility and curative effect of the extract with an appraisal on any possible revitalizing effects on sperm count, morphology, motility, and viability combined with hormonal and histopathological investigations. MATERIALS AND METHODS: Male Wistar rats were used for the study. Two different doses of 400 mg/kg/d and 800 mg/kg/d (both p.o.) of the Hydroalcoholic extract were chosen as test dose while Clomiphene (25 mg/kg/d; p.o.) treatment served as standard treatment. Animals were initially injected with cisplatin (1 mg/kg/d; i.p.) for 15 days and the drug treatment was begun at the 16th day and continued till 43rd day (28 days treatment). Later all male animals got cohabited with female animals in the ratio 1:3. On confirmation of mating, female animals were isolated. Male animals were euthanized on batches. Testis and epididymis were weighed and homogenized. Sperm count, motility, morphology, viability, and headcount. The serum collected was evaluated for serum FSH, LH, and testosterone levels. On day Gestational day 15, gravid uterus observations were calculated to evaluate male and female fertility parameters. RESULTS: There were statistically significant improvements (p < 0.001) in sperm motility, sperm count, sperm viability, and improved morphological features. The same pace was also noticed in testosterone, FSH and LH levels in serum and LPO, CAT, GSH, GPx and SOD in testicular tissues. The extract treated male animals produced better and healthy litter compared to cisplatin-treated animals with less pre- and post-implantation loss. CONCLUSION: Consolidating the results seen, the extract ameliorated the testicular toxicity caused by cisplatin in a dose-dependent manner. Further insight and evaluation of the phytochemicals of the pods should be performed to bring up commercial viability.

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer.

BACKGROUND: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. PATIENTS AND METHODS: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25-75 mg p.o. twice a day; continuous or intermittent), savolitinib (600-800 mg p.o. once a day), or durvalumab (3-10 mg/kg intravenous every 2 weeks). RESULTS: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm-diarrhea (75%), rash (58%), nausea (47%); savolitinib arm-nausea (67%), rash (56%), vomiting (50%); durvalumab arm-rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. CONCLUSION: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. CLINICAL TRIALS NUMBER: NCT02143466.

Structural, biological and pharmaceutical importance of antibiotic agent chloramphenicol.

The vibrational, magnetic resonance and electronic spectral techniques are used to evaluate structural activity associated physico-chemical properties. The biological affinity and drug importance was validated by calculating biological parameters using HyperChem. Mulliken charge assignment for restoring chemical potential for generating drug potential in the molecular site was mapped and analyzed. The vibrational spectral pattern was estimated by identifying active and inactive bands and hindrance of vibrational activity of Acetamide group was monitored and thereby drug malfunction was tested. The chemical reaction pathway around the core carbons of chain and ring was keenly noted and the cause of chemical potential for the inducement of drug mechanism was reported. The stimulation of chemical mechanism for antibiotic activity was addressed by suitable evidence and further improvement for enhancing activity was made. The electronic HOMO and LUMO interaction over different molecular entities are discussed to expose accompany of drug mechanical transitions. The CT complex was recognized to be C=N and C=C bonds and operating drug mechanism was monitored. The unwanted drug property induced by perplexes of charge depletion on α-hydroxyl group was assessed from MEP map. The hyperactive polarization energy of 266.18 X10-33 esu and 327 X10-33 esu of present compound is causing biological activity in good order. The uncontrolled breathing region of Acetamide group was clarified in VCD profile and this is main cause to produce toxicity in drug process.

Structural activity analysis, spectroscopic investigation, biological and chemical properties interpretation on Beta Carboline using quantum computational methods.

In this methodological work, the structural activity analysis have been carried out on ß-Carboline to study the anti cancer activity and the way of improving the biological activity. The molecular spectroscopic tools were used to evaluate all the experimental data like spectral results and data were validated by the computational, HyperChem and Osiris tools. The structural, biological and physico-chemical related analyses have been performed to interpret the properties. The GPCR ligand calculated to be 0.11 for generating pharmacokinetic process, Specified drug information for the compound, was congregated from all types of structural activity which was drawn by spectral and HyperChem data. The σ and π interaction band gap (6.18 eV) ensured the drug consistency. The Mulliken charge process distribution was mapped, the charge orientation assignment was checked; the acquired negative charge potential consignment for the cause of antibiotic impact was verified. The molecular orbital interaction study was carried out to identify the origination of degeneracy of interaction causing drug mechanism. Using NMR spectral pattern, the chemical reaction path was recognized and the nodal region dislocation was distinguished on chemical shift. The Electronegativity (χ) and Electrophilicity charge transfer found to be 3.83 and 0.215, confirmed charge complex transfer for activating drug process in the compound. The molecular nonbonding section was thoroughly observed in order to find the occupancy energy, was the key process to initiate drug activity. The bathochromic electronic shift was observed and the existence of CT complex was discussed. The hindering of toxicity was inspected on inevitable chirality of the compound by specifying VCD spectrum.

Analysis on biological importance of antiseptic drug, O-Benzyl hydroxylamine, by the application of spectroscopic and theoretical tools.

Biological importance of antiseptic drug; O-Benzyl hydroxylamine was explored using QSAR studies for ultimate usage for treating fungal infections. In this research work, the molecular spectroscopic tool and theoretical calculation method of analysis. The data acquired from both tools were evaluated and compared to validate structural and vibrational characteristics. Mulliken charge displacement around molecular site in order for exploring electronic properties to find out the cause of inducement of drug potential. The Lipinski rule of five was evaluated for the measurement of biological importance of the drug compound. The lipophilicity and topological surface area of the drug was monitored for determining biological process activity. The partial involvement of compositional bonds of the molecule was appraised for influential vibrational characteristics. The chemical environment for making chemical property was monitored from the uniform and asymmetrical chemical shift of core and allied carbons. The resultant oscillating potential orientation in the molecular site was identified and the residing zones were recognized to find out the origin of drug potential. The occurrence of CT complex process was studied and the CTC was found to be CC and C-N for generating drug activeness. The enhancement of hyper active polarization was measured in first and second order from which the charge level pulling on different entities were observed for ensuring the biological affinity of the compound. The enantiomer characteristics were thoroughly studied to measure the level of toxicity.

Verifying measurements of residual calcium content in demineralised cortical bone.

Calcium contents of demineralised human cortical bone determined by titrimetric assay and atomic absorption spectrophotometry technique were verified by comparing to neutron activation analysis which has high recovery of more than 90%. Conversion factors determined from the comparison is necessary to correct the calcium content for each technique. Femurs from cadaveric donors were cut into cortical rings and demineralised in 0.5 M hydrochloric acid for varying immersion times. Initial calcium content in the cortical bone measured by titration was 4.57%, only 21% of the measurement by neutron activation analysis; while measured by atomic absorption spectrophotometer was 13.4%, only 61% of neutron activation analysis. By comparing more readings with the measurements by neutron activation analysis with 93% recovery, a conversion factor of 4.83 was verified and applied for the readings by titration and 1.45 for atomic absorption spectrophotometer in calculating the correct calcium contents. The residual calcium content started to reduce after the cortical bone was demineralised in hydrochloric acid for 8 h and reduced to 13% after 24 h. Using the linear relationship, the residual calcium content could be reduced to less than 8% after immersion in hydrochloric acid for 40 h. Atomic absorption spectrophotometry technique is the method of choice for calcium content determination as it is more reliable compared to titrimetric assay.

Crystal property and spectroscopic investigation on electro-optic and physico-chemical properties of NLO crystal; 3-(3,4-Dihydroxyphenyl)-L-Alanine.

In this attempt, in order to obtain high-quality NLO crystal, organic compound; 3-(3,4-Dihydroxyphenyl)-L-Alanine crystal was fabricated. The organic-composite crystal was characterized by crystallographic and spectroscopic tools. The NLO supported parameters like crystal lattice (orthorhombic) and space group (P212121) examined and validated by XRD examination. The SHG test was carried out and SHG efficiency was calculated that1.29 and 1.35 times greater than solid KDP crystal. The laser damage threshold energy density was determined to be 14.51 GW/cm2. By the application of mulliken charge assignment, multiple dielectric cavities were found in crystal material which is able to process the high degree of birefringence gradient. The oscillating chemical potential movement was observed by examining chemical shift, among the core carbons of hexagonal ring and bridge carbons of chain. The chemical softness insists the binding viability of further ligand groups. The π and δ-conjugated interactive complex orbitals recognized on molecular site and participation in optical active mechanism was identified. UV-Visible transmission characteristics of crystal were studied and UV-Visible absorption on degenerate energy states was noted and its band gap energy was estimated. The CT complex of the present case was acknowledged to be COOH group and it causing crystal properties of current organic composite. The hyperactive polarizability was determined as 1775.05 × 10-33 esu and it was found to be five times greater than thiourea. The depletion energy between highly electrophilic zones and protonic zones was estimated to be ±5.241 e 2 causing permanent dielectric characteristics for the title organic composite. The non-superposable on the molecular mirror image was displayed and thereby optical ability was validated.

Quantifying the ultrastructure changes of air-dried and irradiated human amniotic membrane using atomic force microscopy: a preliminary study.

Air-dried and sterilized amnion has been widely used as a dressing to treat burn and partial thickness wounds. Sterilisation at the standard dose of 25 kGy was reported to cause changes in the morphological structure as observed under the scanning electron microscope. This study aimed to quantify the changes in the ultrastructure of the air-dried amnion after gamma-irradiated at several doses by using atomic force microscope. Human placentae were retrieved from mothers who had undergone cesarean elective surgery. Amnion separated from chorion was processed and air-dried for 16 h. It was cut into 10 × 10 mm, individually packed and exposed to gamma irradiation at 5, 15, 25 and 35 kGy. Changes in the ultrastructural images of the amnion were quantified in term of diameter of the epithelial cells, size of the intercellular gap and membrane surface roughness. The longest diameter of the amnion cells reduced significantly after radiation (p < 0.01) however the effect was not dose dependent. No significant changes in the shortest diameter after radiation, except at 35 kGy which decreased significantly when compared to 5 kGy (p < 0.01). The size of the irradiated air-dried amnion cells reduced in the same direction without affecting the gross ultrastructure. At 15 kGy the intercellular gap decreased significantly (p < 0.01) with Ra and Rq, values reflecting surface roughness, were significantly the highest (p < 0.01). Changes in the ultrastructure quantified by using atomic force microscope could complement results from other microscopic techniques.

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer.

Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Design: Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results: Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents. Conclusions: Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.