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Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

Ovarian cancer (OC) is the most lethal gynecological malignancy among women worldwide. In most cases, it is diagnosed late at an advanced stage and does not respond well to existing therapies leading to its poor prognosis. In addition, other factors including epidemiological, complex histological diversity, multiple molecular alterations, and overlapping signaling pathways are also important contributors to poor disease outcome. Efforts have continued to develop a deeper understanding of the molecular pathogenesis and altered signaling nodes that provide hope for better clinical management through the development of novel approaches for early diagnosis, disease subtyping, prognosis, and therapy. In this chapter, we provide a detailed overview of OC and its histological subtypes and discuss prevalent molecular aberrations and active signaling pathways that drive OC progression. We also summarize various diagnostic and prognostic markers and therapeutic approaches currently being employed and discuss emerging findings that hold the potential to change the future course of OC management.

The development of cancer is not just the growth and proliferation of a single transformed cell, but its surrounding environment also coevolves with it. Indeed, successful cancer progression depends on the ability of the tumor cells to develop a supportive tumor microenvironment consisting of various types of stromal cells. The interactions between the tumor and stromal cells are bidirectional and mediated through a variety of growth factors, cytokines, metabolites, and other biomolecules secreted by these cells. Tumor-stromal crosstalk creates optimal conditions for the tumor growth, metastasis, evasion of immune surveillance, and therapy resistance, and its targeting is being explored for clinical management of cancer. Natural agents from plants and marine life have been at the forefront of traditional medicine. Numerous epidemiological studies have reported the health benefits imparted on the consumption of certain fruits, vegetables, and their derived products. Indeed, a significant majority of anti-cancer drugs in clinical use are either naturally occurring compounds or their derivatives. In this review, we describe fundamental cellular and non-cellular components of the tumor microenvironment and discuss the significance of natural compounds in their targeting. Existing literature provides hope that novel prevention and therapeutic approaches will emerge from ongoing scientific efforts leading to the reduced tumor burden and improve clinical outcomes in cancer patients.

Rajashekhar Kanchanapally,1 Sachin Kumar Deshmukh,1 Suhash Reddy Chavva,1 Nikhil Tyagi,1 Sanjeev Kumar Srivastava,1 Girijesh Kumar Patel,1 Ajay Pratap Singh,1,2 Seema Singh1,2 1Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA; 2Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA Background: Despite tremendous advancement, cancer still remains one of the leading causes of death worldwide. Inefficiency of current drug delivery regimens is one important factor that limits the therapeutic efficacy of existing drugs, thus contributing to cancer mortality. To address this limitation, synthetic nanotechnology-based delivery systems have been developed; however, they raise concern of inducing adverse immunogenic reactions. Exosomes (Exos) are nonimmunogenic nano-sized vesicles that have received significant attention as efficient drug delivery system. Methods: Drug loading in Exos were achieved by incubating different cell types viz pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs), and macrophages (MØs) with Doxorubicin (DOX). Differential ultracentrifugation was performed to isolate exosome and their size was determined by dynamic light scattering analysis. The efficacy of drug packaging into Exos was evaluated by HPLC. Flow cytometry was performed to examine the apoptosis. Cell viability was determined using the WST-1 assay.Results: PCCs shed the most Exos and were the most efficient in drug loading followed by MØs and PSCs as examined by HPLC quantification. However, when compared for antitumor efficacy, MØ-derived Exos loaded with DOX (MØ-Exo-DOX) showed highest activity followed by PSCs and PCCs. Conclusion: These varying antitumor activities likely resulted from nondrug contents of Exos since we did not observe any significant differences in their uptake by the cancer cells. Altogether, our data suggest that donor cell-specific differences exist in Exos, which could influence their utility as drug carrier for therapeutic purposes. Keywords: exosome, macrophage, pancreatic cancer, drug delivery, doxorubicin

Ovarian cancer (OC) is the most lethal gynecological malignancy, which disproportionately affects African American (AA) women. Lack of awareness and socioeconomic factors are considered important players in OC racial health disparity, while at the same time, some recent studies have brought focus on the genetic basis of disparity as well. Differential polymorphisms, mutations and expressions of genes have been reported in OC patients of diverse racial and ethnic backgrounds. Combined, it appears that neither genetic nor the socioeconomic factors alone might explain the observed racially disparate health outcomes among OC patients. Rather, a more logical explanation would be the one that takes into consideration the combination and/or the interplay of these factors, perhaps even including some environmental ones. Hence, in this article, we attempt to review the available information on OC racial health disparity, and provide an overview of socioeconomic, environmental and genetic factors, as well as the epigenetic changes that can act as a liaison between the three. A better understanding of these underlying causes will help further research on effective cancer management among diverse patient population and ultimately narrow health disparity gaps.

Breast cancer (BC) continues to be the most frequently diagnosed cancer in American women, which disproportionately affects women of African-American (AA) descent. Previously, we reported greater serum levels of resistin in AA BC patients relative to Caucasian-American (CA) patients, and established its role in growth and aggressiveness of breast tumor cells. Here we have investigated the role of resistin in BC-chemoresistance. MDA-MB-231 and MDA-MB-468 BC cells of CA and AA origin, respectively, were incubated with resistin prior to doxorubicin treatment. Our data suggest that resistin conferred chemoresistance to both BC cell lines; however, the effect on AA cells was more profound. Furthermore, the resistin-induced doxorubicin-resistance was shown to occur due to suppression of apoptosis. Resistin treatment also affected the stemness of BC cells, as suggested by reduced cell surface expression of CD24, induced expression of CD44 and ALDH1, and increased capability of cells to form mammospheres. Mechanistic studies revealed that resistin-induced chemoresistance, apoptosis and stemness of BC cells were mediated through STAT3 activation. Taken together, our findings provide novel insight into the role of resistin in BC biology, and strengthen its role in racially disparate clinical outcomes.

In the present communication we theoretically investigate and study the properties of defect modes in one dimensional defective photonic crystal (PC) based on magnetic fluid film (MFF). The magnetic fluid film (MFF) is a type of stable colloidal suspensions of magnetic nanoparticles. When the MFF is subjected to an external applied magnetic field, the nanoparticles form a chain along certain direction of magnetic field and its refractive index changes; this property of MFF can be used to tune the defect modes (transmission peaks) in PC. In this study, first, we take a PC structure composed of alternate layers of TiO2 and SiO2 and MFF (water based MnFe2O4 nanoparticles) as a defect layer having different porosity. In second case we take, two symmetric PC structure composed of alternate layers of MFF with different porosity and the effect of magnetic field on the surface mode (acts as a defect mode) has been studied. In order to calculate transmission spectra, we use transfer matrix method (TMM). Investigation of transmission curves show that tunability of defect modes (transmission peaks) are greatly influenced by magnetic field factor as well as the porosity of magnetic fluid film. This type of PC structure can be used to design the optical devices such as magnetic field sensors, tunable optical grating, optical switches, tunable narrow transmission filter, wavelength division multiplexer etc.

Prostate cancer is the mostly commonly diagnosed non-cutaneous malignancy and the second leading cause of cancer-related death affecting men in the United States. Moreover, it disproportionately affects the men of African origin, who exhibit significantly greater incidence and mortality as compared to the men of European origin. Since androgens play an important role in the growth of normal prostate and prostate tumors, targeting of androgen signaling has remained a mainstay for the treatment of aggressive prostate cancer. Over the years, multiple approaches have been evaluated to effectively target the androgen signaling pathway that include direct targeting of the androgens, androgen receptor (AR), AR co-regulators or other alternate mechanisms that impact the outcome of androgen signaling. Several of these approaches are currently in clinical practice, while some are still pending further development and clinical evaluation. This remarkable progress has resulted from extensive laboratory, pre-clinical and clinical efforts, and mechanistic learnings from the therapeutic success and failures. In this review, we describe the importance of androgen signaling in prostate cancer biology and advances made over the years to effectively target this signaling pathway. We also discuss emerging data on the resistance pathways associated with the failure of various androgen signaling- targeted therapies and potential of this knowledge for translation into future therapies for prostate cancer.

Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc., have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.

Theoretical investigation of photonic band gaps or reflection bands in one-dimensional annular photonic crystal (APC) containing double negative (DNG) metamaterials and air has been presented. The proposed structure consists of the alternate layers of dispersive DNG material and air immersed in free space. In order to study photonic band gaps we obtain the reflectance spectrum of the annular PC by employing the transfer matrix method (TMM) in the cylindrical waves for both TE and TM polarizations. In this work we study the effect of azimuthal mode number (m) and starting radius (ρ0) on the three band gaps viz. zero averaged refractive index (zero- n ¯ ) gap, zero permittivity (zero- e ) and zero permeability (zero- μ ) gaps. It is found that for m ≥ 1 , zero- μ gap appears in TE mode and zero- e gap appears in TM mode. The width of both zero- μ and zero- e gap increases by increasing m values, but the enhancement of zero- μ gap is more appreciable. Also, the effect of ρ0 on the three band gaps (reflection bands) of annular PC structure at the given m-number has been studied, for both TE and TM polarizations. The result shows that in both polarizations zero- e and zero- μ gaps decreases when ρ0 increases, whereas zero- n ¯ gap remains invariant.

Pancreatic cancer (PC) is the third leading cause of cancer-related death in the United States. It is challenging to treat PC due to the existence of intrinsic and extrinsic chemoresistance mechanisms. We previously reported that honokiol, a phytochemical isolated from Magnolia plant, targets important signaling pathways involved in PC associated with survival, chemoresistance and stromal remodeling, and exhibits significant anti-tumor activity both in vitro and in vivo. However, considering poor bioavailability and tumor uptake as major hurdles in clinical translation, we made efforts to develop an exosomal nanoformulation of honokiol. Mesenchymal cell-derived exosomes are non-immunogenic and express surface markers that could support tumor-targeted delivery. Maximum entrapment of honokiol was achieved when it was used in 1:4 weight ratio with exosomes and subjected to 6 cycles of sonication. Data from dynamic light scattering suggested that key features of exosomes (size, polydispersity and integrity) remained intact post-honokiol encapsulation. The comparative half maximal inhibitory concentration (IC50) data suggested 4 to 5 times greater therapeutic efficacy of exosomal honokiol as compared to that of free honokiol. Similarly, exosomal-honokiol had significantly superior effect on cell cycle progression, apoptosis and expression of cell cycle- and survival-associated proteins than that observed in PC cells treated with equivalent doses of free honokiol. We also found that the cellular uptake of honokiol was significantly greater for exosomal-honokiol as compared to its free form. Together, our work is the first demonstration of exosomal encapsulation of honokiol and its improved anti-tumor efficacy against pancreatic cancer. Citation Format: Mohammad Aslam Khan, Rajashekhar Kanchanapally, Sachin Kumar Deshmukh, Sanjeev K. Srivastava, Seema Singh, Ajay P. Singh. Exosomal formulation escalates cellular uptake of honokiol leading to enhanced antitumor efficacy in pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6259.

In this paper, we present the theoretical investigation and study of reflectance properties in a 1D ternary annular photonic crystal (TAPC) containing a semiconductor and a high-temperature superconductor. The proposed structure consists of alternate layers of indium nitride (InN), Bi2Sr2CaCu3O8 (BSCCO), and air placed in free space. A reflectance spectrum of the TAPC is obtained by employing the transfer matrix method (TMM) in the cylindrical waves for both transverse electric (TE) and transverse magnetic (TM) polarized waves. From the study of reflectance spectra, it is observed that the reflection band of the annular photonic crystal depends on the azimuthal mode number m in addition to other parameters. It is found that for azimuthal mode number m = 0, the width of the reflection band of the annular photonic crystal is the same as that of a planar photonic crystal (PPC). When the azimuthal mode number increases, the width of the reflection band increases at higher m values (m >5) for TE waves. In the case of the TM wave, it is interesting to observe that a superpolariton gap is created for a higher value of the azimuthal number (m >0). Further, we see the effect of the starting radius (ρ 0) on the reflection band of the TAPC structure at the given m number for both TE- and TM-polarized waves. Finally, the effect of temperature on the reflectance spectra for both TE and TM waves at the given ρ 0 and azimuthal mode has been studied.

Background: MYB encodes for a transcription factor regulating the expression of a wide array of genes involved in cellular functions. It is reported to be amplified in a sub-set of pancreatic cancer (PC) cases; however, its pathobiological association has remained unclear thus far. Methods: Expression of MYB and other cellular proteins was analysed by immunoblot or qRT-PCR analyses. MYB was stably overexpressed in non-expressing (BxPC3) and silenced in highly expressing (MiaPaCa and Panc1) PC cells. Effect on growth was analysed by automated cell counting at 24-h interval. Cell-cycle progression and apoptotic indices of PC cells with altered MYB expression were measured through flow cytometry upon staining with respective biomarkers. Cell motility/invasion was examined in a Boyden's chamber assay using non-coated or Matrigel-coated membranes. Effect on tumorigenicity and metastatic potential was examined by non-invasive imaging and through end-point measurements of luciferase-tagged MYB-altered PC implanted in the pancreas of nude mice. Results: MYB was aberrantly expressed in all malignant cases of pancreas, whereas remained undetectable in normal pancreas. All the tested established PC cell lines except BxPC3 also exhibited MYB expression. Forced expression of MYB in BxPC3 cells promoted their growth, cell-cycle progression, survival and malignant behaviour, whereas its silencing in MiaPaCa and Panc1 cells produced converse effects. More importantly, ectopic MYB expression was sufficient to confer tumorigenic and metastatic capabilities to non-tumorigenic BxPC3 cells, while its silencing resulted in significant loss of the same in MYB-overexpressing cells as demonstrated in orthotopic mouse model. We also identified several MYB-regulated genes in PC cells that might potentially mediate its effect on tumour growth and metastasis. Conclusions: MYB is aberrantly overexpressed in PC cells and acts as a key determinant of pancreatic tumour growth and metastasis.

// Mohammad Aslam Khan 1, * , Sanjeev K. Srivastava 1, * , Arun Bhardwaj 1 , Seema Singh 1 , Sumit Arora 1 , Haseeb Zubair 1 , James E. Carter 2 , Ajay P. Singh 1, 3 1 Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA 2 Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA 3 Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama, USA * These authors have contributed equally to this work Correspondence to: Ajay P. Singh, e-mail: asingh@health.southalabama.edu Keywords: pancreatic cancer, gemcitabine, angiogenesis, IL-8 Received: March 11, 2015 Accepted: April 10, 2015 Published: April 23, 2015 ABSTRACT Pancreatic tumor microenvironment (TME) is characterized by poor tumor-vasculature and extensive desmoplasia that together contribute to poor response to chemotherapy. It was recently shown that targeting of TME to inhibit desmoplasiatic reaction in a preclinical model resulted in increased microvessel-density and intratumoral drug concentration, leading to improved therapeutic response. This approach; however, failed to generate a favorable response in clinical trial. In that regard, we have previously demonstrated a role of gemcitabine-induced CXCR4 signaling as a counter-defense mechanism, which also promoted invasiveness of pancreatic cancer (PC) cells. Here, we investigated the effect of gemcitabine on endothelial cell phenotype. Gemcitabine-treatment of human-umbilical-vein-endothelial-cells (HUVECs) did not promote the growth of HUVECs; however, it was induced when treated with conditioned media from gemcitabine-treated (Gem-CM) PC cells due to increased cell-cycle progression and apoptotic-resistance. Moreover, treatment of HUVECs with Gem-CM resulted in capillary-like structure (CLS) formation and promoted their ability to migrate and invade through extracellular-matrix. Gemcitabine-treatment of PC cells induced expression of various growth factors/cytokines, including IL-8, which exhibited greatest upregulation. Further, IL-8 depletion in Gem-CM diminished its potency to promote angiogenic phenotypes. Together, these findings suggest an indirect effect of gemcitabine on angiogenesis, which, in light of our previous observations, may hold important clinical significance.

Gynecological cancers (GCs) are often diagnosed at advanced stages, limiting the efficacy of available therapeutic options. Thus, there remains an urgent and unmet need for innovative research for the efficient clinical management of GC patients. Research over past several years has revealed the enormous promise of miRNAs. These small non-coding RNAs can aid in the diagnosis, prognosis and therapy of all major GCs, viz., ovarian cancers, cervical cancers and endometrial cancers. Mechanistic details of the miRNAs-mediated regulation of multiple biological functions are under constant investigation, and a number of miRNAs are now believed to influence growth, proliferation, invasion, metastasis, chemoresistance and the relapse of different GCs. Modulation of tumor microenvironment by miRNAs can possibly explain some of their reported biological effects. miRNA signatures have been proposed as biomarkers for the early detection of GCs, even the various subtypes of individual GCs. miRNA signatures are also being pursued as predictors of response to therapies. This review catalogs the knowledge gained from collective studies, so as to assess the progress made so far. It is time to ponder over the knowledge gained, so that more meaningful pre-clinical and translational studies can be designed to better realize the potential that miRNAs have to offer.

Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences. Tumor microenvironment, which provides a favorable niche for the growth of tumor cells, is comprised of several types of stromal cells and the various proteins secreted as a consequence of bi-directional tumor-stromal cross-talk. Emerging evidence suggests inherent biological differences in the tumor microenvironment of breast cancer patients from different racial backgrounds. Tumor microenvironment components, affected by the genetic make-up of the tumor cells as well as other non-tumor-associated factors, may also render patients more susceptible to the development of aggressive tumors and faster progression of disease resulting in early onset, thus adversely affecting patients' survival. This review provides an overview of breast cancer racial disparity and discusses the existence of race-associated differential tumor microenvironment and its underlying genetic and non-genetic causal factors. A better understanding of these aspects would help further research on effective cancer management and improved approaches for reducing the racial disparities gaps in breast cancer patients.

Breast cancer is the most commonly diagnosed malignancy and a leading cause of cancer-related death in women worldwide. It also exhibits pronounced racial disparities in terms of incidence and clinical outcomes. There has been a growing interest in research community to better understand the role of the microenvironment in cancer. Several lines of evidence have highlighted the significance of chronic inflammation at the local and/or systemic level in breast tumor pathobiology. Inflammation can influence breast cancer progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Targeting of immune and inflammatory pathways has met tremendous success in some cancers underscoring the importance of research to further our understanding of these systems in breast cancer. This knowledge can be helpful not only in the development of novel prevention and therapeutic strategies, but also help in better prediction of therapeutic responses in patients. This review summarizes some of the significant findings on the role of inflammation in breast cancer to gain collective molecular and mechanistic insights. We also discuss ongoing efforts and future outlook to exploit the existing knowledge for improved breast cancer management.

Enhancement of the reflection bands in ultraviolet region by using one-dimensional multi quantum well (MQW) photonic crystal (PC) structure has been investigated theoretically. The proposed structure is composed of three MgF2/SrTiO3 MQWs. The range of reflection band is investigated from the reflectance spectra of the one-dimensional MQW photonic crystal structure obtained by Transfer Matrix Method (TMM). From the numerical analysis it is observed that a range of reflection band for a single MQW PC is very narrow though it increases as the thickness of layers increases. But when three MQWs of MgF2/SrTiO3 are used we get much enlarged reflection band covering the range 119.8 nm- 311.3 nm (reflectivity > 99%) with bandwidth 191.5 nm, for normal incidence. Further, we see that when the angle of incidence is increased, the width of reflection band increases in case of TE wave with a decrease for TM wave, because this omnidirectional reflection (ODR) band is very much narrow in UV region. We have computed ODR band upto incidence angle 50 ◦ for single as well as combined MQW PC. Analyzing the reflectance curve for incidence angle up to 50 ◦ for both TE and TM polarizations we find that by applying the combined MQW PC, omnidirectional reflection band increases significantly in comparison to single MQW structure. The proposed MQW photonic crystal structure is very useful in designing ultraviolet shielding for drugs, ultraviolet reflector for protecting damage of DNA and in skin diseases especially for skin cancer.

The present paper describes the study of defect modes in a one-dimensional photonic crystal (1d-PC) containing a high and low temperature superconductor as a defect layer at different temperatures below the superconducting transition temperature (T c ). Since the refractive index of the superconducting material is dependent on the penetration depth, which depends on the temperature of the superconducting material, hence by changing the temperature of the superconducting material its refractive index can also be changed. Analysis of the transmission spectra of defect modes in the reflection band of 1d-PC structure shows a shift in the wavelength peak of the defect mode. The shift in peak is different for different superconducting materials and it increases with the increase in temperature whether the defect layer is high T c or low T c superconductors. We also study the presence two defect layers in a 1d-PC structure, one with high T c and other with a low T c superconductor. Further, the effect of variation in the thickness of the defect layer on the defect modes of the PC structure has also been studied In order to obtain the transmission (reflection) spectra of a 1d-PC structure with a defect, we employ the transfer matrix method (TMM). This property of the defective PC structure can be exploited in designing the temperature sensor and narrow optical filters. Further, this tunable feature of superconductor photonic crystal has technical use in the superconducting electronics and photonics.

The present paper describes the theoretical investigation of enlarged reflection bands (photonic band gaps) in a 1D star waveguide (SWG) structure consists of superconductor and dielectric as its constituent materials. For the present study, we take the different combinations of superconductor and dielectric materials as a backbone and side branches of the SWG structure. In order to obtain the dispersion relation, Interface Response Theory (IRT) has been employed. Photonic band gaps of SWG structure having superconductor–superconductor, superconductor–dielectric, and dielectric–superconductor materials are compared with the band gaps of the conventional photonic crystal (PC) structure having superconductor–superconductor and dielectric–superconductor materials. Analysis of the dispersion characteristics shows that there exists no band gaps for conventional PC when both layers are made of the same superconducting materials (as the usual case) while the SWG structure shows forbidden bands of finite width even the backbone and side branches are made of same materials. Also, the SWG structure having superconductor–dielectric shows the wider reflection bands in comparison with the structure having dielectric–superconductor as its constituent materials, while for the conventional PC structure it is same in both the cases. Further, the effect of temperature and the effect of variation of number of grafted branches on the photonic bands of SWG structure have been studied.

In the present communication, we have theoretically investigated and studied the reflection properties of one-dimensional birefringent-dielectric photonic crystal (1D BDPC) structure consisting alternate layers of BD material. From the analysis of the reflectance spectra it is found that 100% reflection region for both TEand TMmode can be enhanced significantly in comparison with 1D dielectricdielectric photonic crystal (DDPC). In order to obtain the reflection spectra of the proposed structure we have used the transfer matrix method (TMM). The structure proposed by us, has a wider omnidirectional reflection (ODR) range in comparison to conventional all dielectric photonic crystals (PCs). The width of ODR can be enlarged by considering the suitable choice of lattice parameters.

We show theoretically that range of reflection bands and defect modes inside the band gap can be tuned by using a one-dimensional tilted photonic crystal (TPC) structure. A TPC structure is similar to the conventional PC structure with the only difference that in this case alternate layers are inclined at certain angle in the direction of periodicity of the structure. In order to obtain the reflectance spectra of the proposed structure transfer matrix method (TMM) has been employed. From the analysis of the reflectance curve, it is found that 100% reflectance range can be varied and enhanced by using TPC structure for both (TE- and TM-) polarizations. The enhancement in reflection bands increases as the tilt angle increases for both the polarizations and hence the enlarged omni-reflectance bands are obtained. Further, we study the properties of the defect modes in TPC structure by introducing the tilted defect at the different tilt angle. The results show that defect modes (tunneling modes) can be tuned at different wavelengths by changing the tilt angle of the structure without changing other parameters. Finally, the effect of variation thickness of defect layers on the tunneling mode has been studied for both TPC and conventional PC structure. The proposed model might be used as a tunable broadband omnidirectional reflector as well as tunable tunneling or transmission mode, which has potential applications in the field of photonics and optoelectronics.

Background: Pancreatic cancer cells are highly resistant to drug therapy; however, underlying causes remain largely unknown. We hypothesised that the activation of CXCL12–CXCR4 signalling confers drug resistance to pancreatic cancer cells by potentiating survival. CXCR4 is overexpressed in precancerous/malignant pancreatic lesions and cancer stem cells, and implicated in its pathogenesis. Methods: Effect of CXCR4 activation by CXCL12 on restricting the gemcitabine-induced cytotoxicity and stimulating the survival signalling was examined in pancreatic cancer cells by MTT, DNA laddering, caspase activity, immunoblot, and promoter-reporter assays. Subsequently, we examined the effect of CXCR4 antagonist, AMD3100, in abrogating the rescue effect of activated CXCL12–CXCR4 signalling. Results: The pancreatic cancer cells treated with gemcitabine exhibited reduced cytotoxicity in the presence of CXCL12 as compared with the cells treated with drug alone. CXCL12 induced the activation of FAK, ERK, and Akt signalling pathways, enhanced transcriptional activities of β-catenin and NF-κB, and expression of survival proteins. AMD3100 arrested the CXCL12-induced pancreatic cancer cell growth and drug resistance. Conclusion: Our findings demonstrate, for the first time, a role of CXCL12–CXCR4 signalling axis in conferring drug resistance to pancreatic cancer cells and suggest that it could serve as a novel therapeutic target for pancreatic cancer therapy, alone and in combination with the cytotoxic drug.

The reflectivity of one-dimensional chalcogenide photonic crystal (CGPC) structure with the first order reflection band in near infrared (NIR) region is theoretically studied. Sb-Se and Ge-S chalcogenide glasses are used as high and low refractive index layers respectively, because these materials have zero absorption in NIR region. The transfer matrix method (TMM) is employed to calculate the reflective spectra of the proposed structure. The theoretical results of reflective spectra of bulk chalcogenide materials with the composition of Sb40Se60 and Ge30S70 for 4, 8, 12 and 15 layers and thicknesses of 117 nm and 183 nm respectively, at normal incidence, are close agreement with the experimental results. Furthermore, by increasing the number of layers of Sb40Se60 and Ge30S70, the reflection bands can be enhanced in the wider range of the NIR region for the polarization at different angles and thus the broadband omnidirectional reflector can be designed.

Resistance to chemotherapeutic drugs remains a major cause of therapeutic failure in pancreatic cancer (PC) patients. Efficacy of chemotherapy is further limited by its debilitating effects on immune system. Apart from genetic abnormalities in tumor cells, the tumor immune- microenvironment plays a crucial role in PC chemoresistance. However, it is unclear how chemotherapy affects the cancer immunity or how it affects the tumor microenvironment (TME). In the present study, we demonstrate gemcitabine induces an increased infiltration of CD68+ M2 macrophages in pancreatic tumors isolated from an orthotopic xenograft murine model. Moreover, the conditioned media from PC cell lines cultured with gemcitabine (Gem-CM) promotes migration, invasion, and growth of RAW264.7 macrophage. Interestingly, Gem-CM induces an upregulation of tumor-associated or M2-polarized macrophage markers, arginase-1 and TGF-β1. Additionally, gemcitabine treatment of PC cell lines induces the expression of M2-polarization associated cytokines, growth factors and chemokines, including IL-8. IL-8 exhibits the greatest upregulation after culture with Gemcitabine. Further, IL-8 neutralization in Gem-CM diminished its ability to induce growth, migration, and invasion of RAW264.7 macrophages. Together, these findings suggest an indirect effect of gemcitabine on increasing macrophage trafficking and M2-polarization that potentially supports a pro-tumor microenvironment. These actions may contribute to the chemoresistance of PC. Prevention of gemcitabine-induced macrophage infiltration, growth and M2-polarization will offer a better strategy to counter chemotherapy-induced immunosuppression in PC. Citation Format: Sachin Kumar Deshmukh, Arun Bhardwaj, Nikhil Tyagi, Mohammad Aslam Khan, Sanjeev K. Srivastava, Ahmed AL-Ghadhban, Kari Dugger, James E. Carter, Ajay P. Singh, Seema Singh. Gemcitabine treatment induces immunosuppressive microenvironment in pancreatic cancer by promoting the infiltration, growth, and polarization of macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 113.

We propose the design of broadband optical reflector using a one-dimensional graded photonic crystal (GPC) structure. The proposed structure consists of a periodic array of two alternate layers of SiO2 and Si with low and high values of refractive indices (n 1 and n 2) and thicknesses a and b, respectively. The GPC structure considered here has a linear change in the thickness of the constituent layers for a certain number of layers and has a periodic repetition of this unit. In order to calculate the reflection properties a transfer matrix method (TMM) has been used. This investigation shows that GPC structures have wider reflection bands in comparison to a conventional PC structure and the width of the reflection bands can be enlarged by increasing the number of graded periods and also by increasing the thickness of periods. We also observe that in a GPC structure, omnidirectional reflection (ODR) bands get enhanced without increasing the number of layers of the structure. Hence, a GPC structure can be ...

In this paper, we study the photonic band structure and reflection properties in one-dimensional magnetic photonic crystals (MPCs). Investigation of dispersion characteristics shows that in the case of MPCs, photonic band gaps arise due to the contrast in the wave impedance, not due to the contrast in the refractive index, while contrast in the refractive index of the two layers decides the position and number of the band gaps. We also study the effect of permittivity and permeability on reflection bands, which shows that the structure that has larger values of magnetic permeability (μ) than dielectric permittivity (e) have wider TM-reflection bands, whereas the structure for which e is greater than μ has wider TE-reflection bands. But the gap to mid-gap frequency ratio for TM-reflection bands is larger than TE-reflection bands. Thus, magnetic permeability has greater impact on the reflectivity of MPCs than dielectric permittivity. Finally, the analysis of the omni-reflectance in MPCs has also been studied.

In the present paper, we have made an analysis to observe the effect of introduction of defect on dispersion relation, group velocity, and effective group index in a conventional photonic band gap (PBG) structure. The study shows that inside the PBG materials group velocity and effective group index becomes negative in both types (conventional as well as defect PBG structure) of structure at a certain range of frequencies. Also, near the edges of the bands it attains very high values of index of refraction. A defect PBG structure gives a very unique feature that group velocity becomes exactly zero at a particular value of frequency and also becomes several hundred times greater than the velocity of light which is not attainable with the conventional PBG structure. Defect PBG structures with such peculiar characteristics are seen in lasing without inversion, in construction of perfect lens, in trapping of photon and other optical devices.

In the present communication, we investigate theoretically and study a different type of photonic structure called metallic star waveguide (SWG) structure. The proposed structure, having single homogenous metallic material, is composed of a backbone (or substrate) waveguide along which finite side branches grafted periodically. In order to obtain the dispersion relation and hence the photonic band gaps (PBGs) of the SWG structure the Interface Response Theory (IRT) have been applied. Such types of structures show the band gaps without the contrast in the refractive index of the constituent materials. We also show that the range of forbidden bands can be tuned to different value by varying the number grafted branches of the SWG structures, without changing the other parameters. Moreover, the effects of variation of absorption of metals and plasma frequency on the band gaps of the proposed structures have been investigated.

We have studied the optical properties, band structures and group velocities, of one dimensional photonic crystal (1-D PC) containing negative index materials using translational matrix method (TMM). The 1-D PC containing negative index materials is a periodic arrangement of positive index material (PIM) and negative index material (NIM). The observed group velocity of such structure is larger than the speed of light in certain range of normalized frequency which shown abnormal behaviors. The group velocity of the PC containing negative index materials have found larger than the speed of light. The values of the group velocity become zero, negative and positive for normalized frequencies. The structure containing negative index

In this paper we show, theoretically, that total omnidirec- tional reflected frequency band is enlarged considerably by using one- dimensional photonic crystal (PC) structure composed of alternate lay- ers of ordinary material (OM) and left handed material (LHM). From the analysis it is found that the proposed structure has very wide range of omnidirectional total frequency bands for both polarizations in com- parison to the normal PC structure, which consists of alternate layers of ordinary material having positive index of refraction. The proposed structure also has an absolute band gap that can be exploited to trap the light.

We study the omnidirectional reflection (ODR) in onedimensional photonic crystal (PC) structures consisting of alternate layers of fullerene-gallium arsenide (GaAs), fullerene-germanium (Ge) and fullerene-telurium (Te). The proposed structures give 100% reflection within a very wide range of wavelength in the visible and in a very narrow portion of near IR region of the EM spectrum. Fullerene (C60) in the form thin film structure is a suitable candidate for the designing the PC structure because alkali-metal doped thin film of fullerene acts as conductor and have almost zero absorption in the wavelength range > 530 nm and near IR region. Also, in this region its dielectric constant has very small dependence on the frequency and can be ignored. Thus being a metallic counter part as well as almost frequency independent dielectric constant and easier fabrication technique it is useful in designing the PC structure. The investigation has also been made for the study the role of ambient medium and effect of number of layers in the formation of ODR.

Pancreatic cancer is a highly lethal malignancy and a fourth leading cause of cancer-related death in the United States. Poor survival of pancreatic cancer patients is largely because of its asymptomatic progression to advanced stage against which no effective therapy is currently available. Over the years, we have developed significant knowledge of molecular progression of pancreatic cancer and identified several genetic and epigenetic aberrations to be involved in its etiology and aggressive behavior. In that regard, recent lines of evidence have suggested important roles of microRNAs (miRNAs/miRs) in pancreatic cancer pathogenesis. microRNAs belonging to a family of small, noncoding RNAs are able to control diverse biological processes due to their ability to regulate gene expression at the posttranscriptional level. Accordingly, dysregulation of miRNAs can lead to several disease conditions, including cancer. There is a long list of microRNAs that exhibit aberrant expression in pancreatic cancer and serve as key microplayers in its initiation, progression, metastasis, and chemoresistance. These findings have suggested that microRNAs could be exploited as novel biomarkers for diagnostic and prognostic assessments of pancreatic cancer and as targets for therapy. This book chapter describes clinical problems associated with pancreatic cancer, roles that microRNAs play in various aspects of pancreatic cancer pathogenesis, and envision opportunities for potential use of microRNAs in pancreatic cancer management.

This paper shows that inside photonic band gap (PBG) materials the effective index of refraction neff, defined in terms of group velocity, becomes negative in a certain range of frequencies. Also, near the photonic-band edge the effective index of refraction neff attains exceptionally high values, which are greater than the refractive indices of the materials (n1 and n2) used. This is related to the anomalous behaviour of group velocity, which becomes negative in a certain range and approaches zero near the photonic-band edge. PBG material with a modified index of refraction has applications in the system of lasing without inversion and can also be used in construction of a perfect lens and other optical devices. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 42: 82–87, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20216

This paper describes the reflectivity properties of layer-by-layer-based photonic band gap (PBG) structures with a defect in their normal structures. The defect is created by the removal of a single material slab. To calculate reflectivity, we use a 2 × 2 matrix formulation. The defective PBG structure gives nearly 100% reflections in the near-infrared region in addition to some parts of the visible region of the wavelengths for all possible angles, and thus acts as broadband reflector. Also, we study the anomalous behavior of the refractive index in these structures and find that the effective refractive index neff ≪ 1 nears the band edges. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 38: 293–297, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11041

Summary The article presents a design of an optical filter using Photonic Band Gap (PBG) materials in the visible and infrared region of the electromagnetic spectrum. This idea is based on the famous Kronig-Penny model in the band theory of solids. The suggested filter may work at any range of the wavelength that can be achieved by choosing the appropriate values of the controlling parameters. This structure is also able to pass the light emitted by the Ruby laser and this acts as a monochromator. Also, we have studied the anomalous behavior of refractive index for the structure having alternate layers of air and GaAs.

Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc-containing endopeptidases, are involved in the tissue remodeling and degradation of the extracellular matrix. MMPs are widely distributed in the brain and regulate various processes including microglial activation, inflammation, dopaminergic apoptosis, blood-brain barrier disruption, and modulation of α-synuclein pathology. High expression of MMPs is well documented in various neurological disorders including Parkinson's disease (PD), Alzheimer's disease (AD), Japanese encephalitis (JE), and Glaucoma. Although potentially critical, the role of MMPs in neuronal disorders is under-investigated. The present review summarizes the role of MMPs in neurodegeneration with a particular emphasis on PD, AD, JE, and Glaucoma.

We theoretically investigate the tunable wavelength selective filter by using one-dimensional photonic crystal (1D PC) with potassium titanyl phosphate (KTP) as a defect layer For this we study the transmission characteristic of the multilayered structure composed of (MgF2/ZnS) N (KTP)/(MgF2/ZnS) N . In order to get the transmittance spectra of defect PC we apply transfer matrix method (TMM). We use KTP crystal as defect layer because it is an electro-optical material and its refractive index changes with the change in the electric field intensity. Due to change in the refractive index, defect modes of the PC structure can be tuned at the desired wavelength. From the analysis of the transmittance spectra it is found that the average change in the central wavelength of defect mode is 0.6 nm/0.01 × 1010 V/m. This property of tunable PC filter can be exploited in designing a wavelength demultiplexer for DWDM application in optical communication.

In this Letter a new analysis of an optical filter using a metallic photonic bandgap material on the microscopic scale is reported. The proposed filter is capable of working over a wide range of the electromagnetic spectrum and the idea is based on the famous Kronig–Penny model in the solid state. The periodic structure consisting of different conducting materials and dielectrics (air) are considered. The structure is also able to pass the light emitted by a He–Ne laser source by choosing the appropriate values of the controlling parameters, and thus this may act as an efficient monochromator. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 68–71, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10518

The fabrication of a bandpass filter in the ultraviolet region of the electromagnetic spectrum with the use of photonic band-gap (PBG) materials is presented on the basis of the Kronig–Penny model in the band theory of solids. The periodic structure of different dielectrics and semiconductor materials in rectangular symmetry is considered. Illustrative diagrams are presented in order of allowed and forbidden bands of wavelengths. The filter can also act as an efficient ultraviolet monochromator by the appropriate selection of the controlling parameters. The anomalous dispersion behavior of glass and zinc sulphide (ZnS) is discussed. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 308–314, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10304

Breast cancer (BC) is most frequently diagnosed cancer and remains the second leading cause of cancer-related deaths in women in the United States. African American (AA) women bear an additional burden of BC with early onset of disease, poorer prognosis, higher risk of recurrence, and worst clinical outcome as compared to Caucasian American (CA) women. Emerging evidence strongly argue the role of tumor-microenvironment (TME) in BC of AA and CA racial backgrounds. On the similar line, our earlier findings suggested that serum levels of resistin; an inflammatory cytokine are significantly elevated in AA BC patients compared to their CA counterparts. Furthermore, we demonstrated that resistin promoted growth and aggressiveness of BC cells. In the present study, we investigated the role of resistin in stemness and chemoresistance of BC cells. For this, two BC cells of CA (MDA-MB-231) and AA (MDA-MB-468) origin were treated with resistin and sphere-forming ability, a key characteristic of cancer stem cells, was determined. Data demonstrate that number of spheres is significantly enhanced in both the BC cells upon resistin stimulation. Immunoblot analyses reveal that resistin-induced sphere-forming ability is associated with enhanced levels of stemness-associated transcription factors (Nanog and KLF4) in BC cells. We next examined if resistin conferred chemoresistance to BC cells. Our data suggest that resistin-treated MDA-MB-231 and MDA-MB-468 BC cells develop greater resistance against doxorubicin-induced cytotoxicity. Notably, the effects conferred by resistin were more prominent in AA BC cells comparing to CA BC cells. Our mechanistic studies unveiled an important role of STAT3 activation in the resistin-induced stemness and chemoresistance of BC cells. Taken together, our findings provide novel insight into the role of resistin in BC biology and further strengthen its role in racially disparate clinical outcomes. Citation Format: Sachin Kumar Deshmukh, Arun Bhardwaj, Sanjeev K. Srivastava, Nikhil Tyagi, Ahmed Al-Ghadhban, Ajay P. Singh, Donna L. Dyess, James E. Carter, Seema Singh. Resistin potentiates stemness and chemoresistance of breast cancer cells through STAT3 activation: implications in breast cancer health disparity [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 949. doi:10.1158/1538-7445.AM2017-949

Despite progress in recent years, pancreatic cancer still remains a major clinical challenge. Its incidence and mortality rates have been on consistent rise, thus underscoring the critical need for novel diagnostic, prognostic and therapeutic tools for its effective management. Recent studies have demonstrated that microRNAs (miRNAs/miRs) are deregulated in a variety of malignancies, including pancreatic cancer, and play a significant role in the initiation, progression and metastasis. Furthermore, their vital involvement in the therapeutic resistance of cancer has also been established. Hence, there has been enormous interest worldwide in investigating the roles of miRNAs in pancreatic cancer pathogenesis and exploiting their utility for clinical benefit. In this review, we summarize current knowledge on the role of miRNAs in pancreatic cancer and discuss their potential use as diagnostic and prognostic biomarkers, and as novel targets for development of effective therapeutic strategies.

Rich dependency structures are often formed in genetic association studies between the phenotypic, clinical, and environmental descriptors. These descriptors may not be standardized, and may encompass various disease definitions and clinical endpoints which are only weakly influenced by various (e.g., genetic) factors. Such loosely defined complex intermediate clinical phenotypes are typically used in follow-up candidate gene association studies, e.g., after genome-wide analysis, to deepen the understanding of the associations and to estimate effect strength. This chapter discusses a solid methodology, which is useful in such a scenario, by using probabilistic graphical models, namely, Bayesian networks in the Bayesian statistical framework. This method offers systematically scalable, comprehensive hierarchical hypotheses about multivariate relevance. We discuss its workflow: from data engineering to semantic publication of the results. We overview the construction, visualization, and interpretation of complex hypotheses related to the structural analysis of relevance. Furthermore, we illustrate the use of a dependency model-based relevance measure, which takes into account the structural properties of the model, for quantifying the effect strength. Finally, we discuss the "interpretational" or translational challenge of a genetic association study, with a focus on the fusion of heterogeneous omic knowledge to reintegrate the results into a genome-wide context.

In the present paper, we theoretically investigate and study the reflection bands and ODR of one- dimensional graded photonic crystal structure having alternate layers of birefringent and dielectric materials for TE and TM polarization.

With the gradual development of intelligence, human got curious to know his origin and evolutionary background. Historical statements and anthropological findings were his primary tool for solving the puzzles of his own origin, until came the golden era of molecular markers which took no time to prove it’s excellence in unveiling answers to the questions regarding the migration pattern of human across different geographical regions. As a bonus these markers proved very much beneficial in solving criminal offences and in understanding the etiology of many dreaded diseases and to design their prevention. In this review, we have aimed to throw light on some of the promising molecular markers which are very much in application now-a-days for not only understanding the evolutionary background and ancient migratory routes of humans but also in the field of forensics and human health.

e23253Background: Acquired resistance to available chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Exosomes, small (50-150 nm) secr...

The present paper describes the study of reflection properties and role of wave impedance in the formation of photonic band gaps in one-dimensional magnetic star waveguide structure (MSWG). From the analysis of the dispersion characteristics, it is found that in magnetic SWG structure existence of band gaps does not require the contrast in the wave impedance of the constituent materials whereas the contrast in wave impedance is must for the existence of band gap in normal magnetic photonic crystal (MPC) structure. Moreover, magnetic SWG structures show wider photonic band gaps in comparison to normal magnetic PC structure for the same contrast in the wave impedance.

CHI3L1 gene encodes for a glycoprotein (HC-gp39 or YKL40) secreted by synovial fibroblasts, macrophages, neutrophil granulocytes and chondrocytes. Its expression is under the control of NF-kB. It is regarded as an acute phase protein, and its levels are significantly elevated in rheumatic diseases. Furthermore, HC-gp39 has been shown to be recognized by autoreactive T cells in rheumatoid arthritis. In the present study, we have examined two functional variants of the promoter region of CHI3L1 gene (CHI3L1-1 (rs4950928) and CHI3L1-2 (rs10399931) that have been reported earlier to be associated with schizophrenia and sarcoidosis. We used TaqMan allelic discrimination assays to study the genotypes of Hungarian patients with rheumatoid arthritis (n = 182) and of healthy controls (n = 194). No significant association of the investigated SNPs with the disease was found. Here we report that CHI3L1 SNPs, shown to be involved in the predisposition of schizophrenia, are not associated with rheumatoid arthritis.