Endometriosis, an incurable gynecological disease that causes abnormal growth of uterine-like tissue outside the uterine cavity, leads to pelvic pain and infertility in millions of individuals. Endometriosis can be treated with medicine and surgery, but recurrence and comorbidities impair quality of life. In recent years, nanoparticle (NP)-based therapy has drawn global attention, notably in medicine. Studies have shown that NPs could revolutionize conventional therapeutics and imaging. Researchers aim to enhance the prognosis of endometriosis patients with less invasive and more effective NP-based treatments. This study evaluates this potential paradigm shift in endometriosis management, exploring NP-based systems for improved treatments and diagnostics. Insights into nanotechnology applications, including gene therapy, photothermal therapy, immunotherapy, and magnetic hyperthermia, offering a theoretical reference for the clinical use of nanotechnology in endometriosis treatment, are discussed in this review.

Abstract Background Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models. Methods The cytotoxicity of JAK/HDACi, regorafenib, and their combination were tested with normal colonic and CRC cells exhibiting various genetic backgrounds. Kinomic, ATAC-seq, RNA-seq, cell cycle, and apoptosis analyses were performed to evaluate the cellular functions/molecular alterations affected by the combination. Efficacy of the combination was assessed using patient-derived xenograft (PDX) and experimental metastasis models of CRC. To evaluate the interplay between tumor, its microenvironment, and modulation of immune response, MC38 syngeneic mice were utilized. Results The combination therapy decreased cell viability; phosphorylation of JAKs, STAT3, EGFR, and other key kinases; and inhibited deacetylation of histone H3K9, H4K8, and alpha tubulin proteins. It induced cell cycle arrest at G0-G1 phase and apoptosis of CRC cells. Whole transcriptomic analysis showed that combination treatment modulated molecules involved in apoptosis, extracellular matrix-receptor interaction, and focal adhesion pathways. It synergistically reduces PDX tumor growth and experimental metastasis, and, in a syngeneic mouse model, the treatment enhances the antitumor immune response as evidenced by higher infiltration of CD45 and cytotoxic cells. Pharmacokinetic studies showed that combination increased the bioavailability of regorafenib. Conclusions The combination treatment was more effective than with regorafenib or JAK/HDACi alone, and had minimal toxicity. A clinical trial to evaluate this combination for treatment of mCRCs is warranted.

The study of polymorphism of glutenin makes it possible to identify and isolate desirable genotypes with higher grain quality. In the last few years, only a part of the genetic diversity among the modern and popular wheat germplasm and varieties based on the polymorphism of glutenin subunits are captured. To address this 107 wheat varieties released across different agricultural zones in India, were used to investigate HMW-GS and LMW-GS allele polymorphism, gene diversity and genetic variation in the Glu-1 and Glu-3 loci. Among the different HMW-GS, the highest genetic variation was observed at the Glu-D1 locus with both Glu-D1a and Glu-D1d possessing genetic variation of 0.490, 0.484 respectively. The highest genetic variation at the Glu-A3 locus was observed at the Glu-A3c and GluA3b possessing a genetic variation of 0.463, 0.411 respectively. This was followed by the Glu-B3j having a genetic variation of 0.386 at the Glu-B3 locus. Over 20 years a remarkable increase in the Glu-D1d allele is observed in the newly released varieties in India. Among all the zones, Glu-A1-null is the least frequent allele at the Glu-1 locus, however, it is present as the predominant allele in the NHZ of India. This study elucidates the relationships of these HMW and LMW allelic frequencies and genetic variation with their geographical distribution over the two different periods. This study provides reference data that can be used to assist the breeding, quality evaluation and development of good-quality wheat varieties.

Prostate cancer (PCa) is one of the leading causes of cancer-related death in men worldwide. Chemotherapy is effective in the early management of PCa; long-term use activates drug efflux pumps, resulting in resistance and recurrence. In this context, finding the genetic changes causing PCa development could significantly alter therapeutic results. The approach has been to search for specific molecular targets for the selective elimination of cancer cells. Small molecule inhibitor drugs have successfully targeted cancer cell growth and metastasis promotion. Still, small molecule inhibitors bind to multiple molecular targets, including cell surface receptors and other intracellular proteins, thus increasing the risk of toxicity and having a short life span. Therefore, it is crucial to identify new anti-cancer agents that work with small molecule inhibitors to target cancer cells while preventing normal cells. It has been reported that overexpression of the Thyroid hormone receptor interactor 13 (TRIP13) gene, a critical mitosis regulator, plays a role in many cancers. Our analysis using UALCAN (ualcan.path.uab.edu) showed overexpression of TRIP13 in PCa and it plays a role in PCa biology. When TRIP13 is overexpressed, it phosphorylates EGFR and activates a downstream pathway, making cancer cells more aggressive. Recently, DCZ0415, a small molecule TRIP13 inhibitor, was reported to prevent cell proliferation and invasion in several malignancies. Nevertheless, the therapeutic targeting of TRIP13 driving PCa is not well understood. In this study, we demonstrated Thymoquinone (TQ), a natural compound with multifaceted chemo-preventive potential and anti-cancer agent, could reinforce the effect of DCZ0415 in PCa cell lines (DU145 and PC3). PCa cells were treated with TQ or DCZ0415 alone or combined, followed by cell viability (MTT assay) to determine the optimal IC50 values. In a western blot, RT-qPCR analysis, and flow cytometry assays, the combined drug treatment was most effective in blocking TRIP13, inhibiting cell proliferation, and inducing apoptosis. Furthermore, this study determines the combination can upregulate the expression of cell cycle inhibitor (p21WAF1/CIP1), which, in turn, inhibits the expression of CDK4/Cyclin D1 complex, resulting the cell cycle arrest. In addition, TQ, in combination, downregulates the activation of EGFR-dependent PI3K/Akt-1/ERK1/2 and epithelial-mesenchymal transition (EMT) pathways in both cell lines. In conclusion, these findings show thymoquinone's potential to improve DCZ0415 effectiveness and suggest a new promising anti-cancer strategy for treating patients with prostate cancer. Citation Format: Santosh K. Singh, Manoj K. Mishra, Sooryanarayana Varambally, Rajesh Singh. Enhancing the efficacy of small molecule inhibitor of TRIP13 in prostate cancer using thymoquinone. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4969.

e15597 Background: In the US, colorectal cancer (CRC) is the third most common cancer. Patients receiving regorafenib, a multiple-kinase inhibitor, recommended to manage metastatic CRCs (mCRCs), has a modest improvement in median overall survival but it is associated with several toxicities. Our present study addresses regorafenib-induced toxicity concerns by combining regorafenib with a novel dual JAK-HDAC inhibitor (JAK-HDACi). The rationale for the dual inhibitor drug selection is due to the facts that the JAK/STAT/SOCS pathway is modulated in CRCs, and concurrent inhibition of JAK sensitizes solid tumors to HDACi. This study focused on evaluating the efficacy and reducing regorafenib-induced toxicity with this novel therapeutic combination in CRC preclinical models. Methods: We evaluated the toxicity of the JAK-HDACi, regorafenib, and their combination in normal colonic cells (CRL-1807) and their efficacy in CRC cell lines (HCT116, RKO, HT29, and SW480) exhibiting various statuses of p53, KRAS, BRAF, EGFR, and microsatellite instability, by conducting colony formation, cell proliferation, and cell cycle arrest assays. Kinome profiling and whole transcriptomic analysis were performed. Their efficacy was assessed in vivo in a CRC patient-derived xenograft (PDX) model, and experimental metastasis was evaluated in NSG mice using luciferase-tagged HT29 cells. Non-invasive, whole-body bioluminescence imaging was performed. Tumor tissues were harvested and stored at −80°C or prepared formalin-fixed paraffin-embedded blocks for Hematoxylin and Eosin (H&E) and immunostaining. Serum analysis was performed to evaluate liver and kidney functions to assess the toxicity. Results: At 500 nM concentrations, there was no pronounced death of CRL-1807 cells, but reduced number of colonies in CRC cells. Drug treatments decreased phosphorylation of STAT3 and ERK1/2 and cell viability, wherein the reduction was robust in the combination. The combination reduced activity of various kinases, as evident through kinome profiling. In SW480 cells, the combination caused G0-G1 cell arrest and decreased the S phase. RNA-seq results revealed modulation of key pathways: apoptosis, ECM-receptor interaction, and focal adhesion. The PDX model showed that the combination treatment reduced tumor growth, as evidenced in H&E staining with higher necrosis and reduced Ki67 staining. Experimental metastasis, bioluminescence imaging, and histological examination showed pronounced reduction in metastasis in mice treated with the combination. Serum chemistry profiles showed that the treatments did not cause systemic toxicity to mice used in either model. Conclusions: The combination therapy with the JAK-HDACi and regorafenib was more effective than the single agents with no evident toxicity. These findings lend credence to a clinical trial to assess this combination for treatment of patients with advanced CRC.

Micronutrient and protein malnutrition is recognized among the major global health issues. Genetic biofortification is a cost-effective and sustainable strategy to tackle malnutrition. Genomic regions governing grain iron concentration (GFeC), grain zinc concentration (GZnC), grain protein content (GPC), and thousand kernel weight (TKW) were investigated in a set of 163 recombinant inbred lines (RILs) derived from a cross between cultivated wheat variety WH542 and a synthetic derivative ( Triticum dicoccon PI94624/ Aegilops tauschii [409]//BCN). The RIL population was genotyped using 100 simple-sequence repeat (SSR) and 736 single nucleotide polymorphism (SNP) markers and phenotyped in six environments. The constructed genetic map had a total genetic length of 7,057 cM. A total of 21 novel quantitative trait loci (QTL) were identified in 13 chromosomes representing all three genomes of wheat. The trait-wise highest number of QTL was identified for GPC (10 QTL), followed by GZnC (six QTL), GFeC (three QTL), and TKW (two QTL). Four novel stable QTL ( QGFe.iari-7D.1, QGFe.iari-7D.2, QGPC.iari-7D.2 , and QTkw.iari-7D ) were identified in two or more environments. Two novel pleiotropic genomic regions falling between Xgwm350–AX-94958668 and Xwmc550–Xgwm350 in chromosome 7D harboring co-localized QTL governing two or more traits were also identified. The identified novel QTL, particularly stable and co-localized QTL, will be validated to estimate their effects on different genetic backgrounds for subsequent use in marker-assisted selection (MAS). Best QTL combinations were identified by the estimation of additive effects of the stable QTL for GFeC, GZnC, and GPC. A total of 11 RILs (eight for GZnC and three for GPC) having favorable QTL combinations identified in this study can be used as potential donors to develop bread wheat varieties with enhanced micronutrients and protein.

Background Ovarian cancer (OvCa) is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment for OvCa is surgery and cytotoxic chemotherapy. However, to overcome the high cost and side effects of these treatments, medicinal plants are widely used in developing countries to treat OvCa.Byrsocarpus coccineusplant preparation has been administered to patients traditionally in the management of tumors in Nigeria. In this study, we investigated the anti-proliferative effects ofB. coccineusethanol leaf extract against OVCAR-3 and SW 626 OvCa cell lines. After the treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic, and anti-apoptotic markers. Results Results showed thatB. coccineusethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR-3 and SW 626 treated cells in a dose-dependent manner. Results also show thatB. coccineusethanol leaf extract modulated the expression of tumor suppressor gene (p53), cell cycle progression, pro- and anti-apoptotic gene, and the pro-inflammatory cytokines. Conclusions These results suggest thatB. coccineushave anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.

Despite the improvement in survival for patients with liver cancer (LCa) in recent decades, only one in five patients survive for 5 years after diagnosis. Thus, there is an urgent need to find new treatment options to improve patient survival. For various cancers, including LCa, the chemokine CCL5 (RANTES) facilitates tumor progression and metastasis. Since the function of the CCR5/CCL5 interaction in LCa cell proliferation and migration is poorly understood, the present study was undertaken to investigate the role of the CCR5/CCL5 axis in these processes. Flow cytometry, RT-PCR, Western blot, and immunofluorescence techniques were used to quantify the expression of CCR5 and CCL5 in LCa cells. To determine the biological significance of CCR5 expressed by LCa cell lines, a tissue microarray of LCas stained for CCR5 and CCL5 was analyzed. The results showed higher expression (p < 0.001) of CCR5 and CCL5 in hepatocellular carcinoma (HCC) tissues compared to non-neoplastic liver tissues. Furthermore, to delineate the role of the CCR5/CCL5 interaction in LCa cell proliferation and migration, various LCa cells were treated with maraviroc, a CCR5 antagonist, in the presence of CCL5. These data demonstrated the biological and clinical significance of the CCR5/CCL5 axis in LCa progression. The targeting of this axis is a promising avenue for the treatment of LCa.

African American (AA) men have a higher incidence and greater mortality from prostate cancer (PCa) than Caucasian American (CA) men. The factor influencing the racial disparity is not clearly understood and is probably genetic variation attributed to the disease. Androgen and androgen receptor (AR) pathways have long been associated with prostate growth. Racial differences have also been found among variants of the genes of the enzymes involved in androgen biosynthesis and metabolism, such as CYP3A4, CYP3A7, and CYP17A1. Although several inhibitors are approved for CYPs genes, the major drawback of these inhibitors is they contain the steroid scaffold, which contributes to the undesirable side effects (dyspnea, edema, contusion, etc.) observed in patients. In this regard, using nonsteroid scaffolds such as natural compound acts as a more potent inhibitor and interacts more selectively with the cytochrome P450 family. In this study, our data showed the effect of natural compound thymoquinone (TQ), a constituent of Nigella sativa (black seed), on CYP3A4, CYP3A7, and CYP17A1 genes in PCa cells, and found that TQ-treated cells significantly downregulated the expression of CYP3A4, CYP3A7, and CYP17A1 in MDA PCa 2b and E006AA-hT (African American) compared to LNCaP (Caucasian) cell lines. These findings were further confirmed by flow cytometry, Western blots, and immunofluorescence. These studies suggested that TQ could be the potent inhibitor of the active sites of the cytochrome P450 enzymes, which are an important target in the treatment of PCa. Additionally, knowledge of the PCa susceptibility genes (CYPs) could be used to identify individuals at risk of developing PCa with poor outcomes for heightened screening or prevention modalities and to identify optimal treatment strategies for men of African descent. Citation Format: Santosh K. Singh, James W. Lillard, Jr., Rajesh Singh. Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B70.

Abstract Multidrug-resistance (MDR) is the major reason behind the failure of prostate cancer (PCa) therapy. ATP-binding cassette (ABC) transporters contribute to drug resistance via ATP-dependent drug efflux. P-glycoprotein (Pgp), which is encoded by MDR1 gene, confers resistance to certain anticancer agents. The development of agents able to modulate MDR mediated by Pgp and other ABC transporters remained a major goal for PCa therapy. The proposed study evaluated a novel method for targeted delivery of resveratrol alone or in combination with docetaxel at desired rates for reversal of drug resistance. We described a proprietary planetary ball milling approach (PBM) that uses a natural polysaccharide (starch; FDA approved) to create a drug-polysaccharide nanoparticle as a core that is subsequently coated with novel folate-conjugated poly (ϵ-caprolactone) / poly (ethylene glycol) co-polymer, which allows binding to high-affinity folate receptors presents on PCa cells. The resulting PBM nanoparticles were shown to be rapidly internalized and induce significant cancer cell apoptosis at lower doses compared to unformulated resveratrol and/or docetaxel. Our data showed that resveratrol potently synergizes with docetaxel to inhibit proliferation and induce cell death in resistance PCa cells. The up-regulation of pro-apoptotic (BAX, BID, BAK), p53 and down regulation of anti-apoptotic (BCL-2, MCL-1), Pgp and NF-κB protein confirmed that a synergistic combination of resveratrol-docetaxel with targeted delivery to tumor cells could provide a more potent therapeutic effect at lower drug concentrations and improve the therapeutic index. These results suggested that the co-delivery of resveratrol, and a cytotoxic agent in a PBM nanoparticle might potentially improve the treatment of drug-resistant tumors. [This work is supported from Grant # 5SC1CA193758-03] Citation Format: Santosh K. Singh, James W. Lillard, Rajesh Singh. Reversal of drug resistance in prostate cancer using PBM nanoparticle [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 5867. doi:10.1158/1538-7445.AM2017-5867

Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells. The PCa cell lines DU145 and PC3 were treated with curcumin and docetaxel alone or in combination. After completion of the treatment cell proliferation and the expression of pro-survival and anti-apoptotic markers and the signaling molecules were analyzed. The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone. Interestingly, the combined treatment with curcumin and docetaxel modulates the expression of RTKs, PI3K, phospho-AKT, NF-kappa B, p53, and COX-2. These results suggest that curcumin can be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment.

Prostate cancer (PCa) remains the most common cancer in American men. African-American (AA) men continue to have higher PCa prevalence and mortality rates compared to men in other populations. In addition to socioeconomic factors and lifestyle differences, molecular alterations contribute to this discrepancy. We summarize molecular genetics research results interrelated with the biology of PCa racial disparity. Androgen and androgen receptor (AR) pathways have long been associated with prostate growth. Racial differences have also been found among variants of genes of the enzymes involved in androgen biosynthesis and metabolism. Growth factors and their receptors are a potential cause of the disparity in PCa. Recent molecular and biotechnological approaches in the field of proteomics and genomics will greatly aid the advancement of translational research on racial disparity in PCa, which may help, in finding new prognostic markers and novel therapeutic approaches for the treatment of PCa in AA.

Genomic regions responsible for accumulation of grain iron concentration (Fe), grain zinc concentration (Zn), grain protein content (PC) and thousand kernel weight (TKW) were investigated in 286 recombinant inbred lines (RILs) derived from a cross between an old Indian wheat variety WH542 and a synthetic derivative (Triticum dicoccon PI94624/Aegilops squarrosa [409]//BCN). RILs were grown in six environments and evaluated for Fe, Zn, PC, and TKW. The population showed the continuous distribution for all the four traits, that for pooled Fe and PC was near normal, whereas, for pooled Zn, RILs exhibited positively skewed distribution. A genetic map spanning 2155.3cM was constructed using microsatellite markers covering the 21 chromosomes and used for QTL analysis. 16 quantitative trait loci (QTL) were identified in this study. Four QTLs (QGFe.iari-2A, QGFe.iari-5A, QGFe.iari-7A and QGFe.iari-7B) for Fe, five QTLs (QGZn.iari-2A, QGZn.iari-4A, QGZn.iari-5A, QGZn.iari-7A and QGZn.iari-7B) for Zn, two QTLs (QGpc.iari-2A and QGpc.iari-3A) for PC, and five QTLs (QTkw.iari-1A, QTkw.iari-2A, QTkw.iari-2B, QTkw.iari-5B and QTkw.iari-7A) for TKW were identified. The QTLs together explained 20.0%, 32.0%, 24.1% and 32.3% phenotypic variation, respectively, for Fe, Zn, PC and TKW. QGpc.iari-2A was consistently expressed in all the six environments, whereas, QGFe.iari-7B and QGZn.iari-2A were identified in two environments each apart from pooled mean. QTkw.iari-2A and QTkw.iari-7A, respectively, were identified in four and three environments apart from pooled mean. A common region in the interval of Xgwm359-Xwmc407 on chromosome 2A was associated with Fe, Zn, and PC. One more QTL for TKW was identified on chromosome 2A but in a different chromosomal region (Xgwm382-Xgwm359). Two more regions on 5A (Xgwm126-Xgwm595) and 7A (Xbarc49-Xwmc525) were found to be associated with both Fe and Zn. A QTL for TKW was identified (Xwmc525-Xbarc222) in a different chromosomal region on the same chromosome (7A). This reflects at least a partly common genetic basis for the four traits. It is concluded that fine mapping of the regions of the three chromosomes of A genome involved in determining the accumulation of Fe, Zn, PC, and TKW in this mapping population may be rewarding.

Abstract In order to understanding the molecular mechanisms of drug resistance as well as enhancing the efficacy of docetaxel we established docetaxel-resistant prostate cancer (PCa) cells. The IC50 for docetaxel in PCa resistant cells was about 50-fold higher than parental PCa cells. In the current study we used resveratrol (RES), a natural compound with chemo preventive potential to test its ability to enhance the effectiveness of docetaxel on PCa as well as to explore the mechanism of acquired docetaxel resistance. PCa (PC3, C4-2B and DU145) cell lines treated with different dose of RES or DTX alone or in combination followed by analyzed cell proliferation (MTT assay), apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells and western blot methods).The expression of ABC transporter markers in the development of docetaxel resistance was examined using RT-PCR. Our result shows that the expression of 18 ABC transporter genes were down regulated in PCa cells at 48 and 72 hrs in RES treatment group. The up regulations of pro-apoptotic proteins (Bax, Bad, Bim) and down regulation of anti-apoptotic protein (Bcl2, Mcl1) further confirmed the effectiveness of RES or DTX alone or in combination with DTX. In conclusion these studies suggest that RES inhibits ABC gene expression and resensitizes docetaxel resistant PCa cells to DTX treatment with enhancing apoptotic cell death. Citation Format: Santosh K. Singh, Saswati Banerjee, James W. Lillard, Rajesh Singh. Molecular mechanism of resveratrol induced cell death in multidrug resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5043.

Despite the different prostate cancer (PCa) treatment therapies it continues to be one of the leading causes of death in men. Docetaxel is a well-established chemotherapeutic agent used to target metastatic PCa, however long-term treatment with docetaxel results in drug resistant and toxicity in PCa cells. Combining agents is common to improve outcomes, but the combination should not significantly increase toxicity. Curcumin is a non-toxic natural compound with multifaceted chemo preventive potential. In current study we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cell lines (RWPE-1, C4-2b, DU145 and PC3). PCa cell lines were treated with curcumin or docetaxel alone or in combination followed by cell viability (MTT assay) and apoptosis assay (TUNEL assay and flow-cytometric analysis of annexin V/propidium iodide-stained cells). The expressions of pro- and anti-apoptotic markers were quantitated with real-time PCR and western blot assay. Our results indicate that curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of PCa cells, which was further confirmed by TUNEL assay. The down-regulation of the anti-apoptotic proteins (Bcl2, Mcl-1) and upregulation of pro-apoptotic proteins (Bax, Bid etc.) further confirm that we can considerably reduce docetaxel dose using synergistic combination therapy with curcumin. Thus, our results strongly suggest that we can reduce dose levels of docetaxel and compensate it with non-toxic curcumin and it could be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment. Citation Format: Saswati Banerjee, Santosh K. Singh, James W. Lillard, Rajesh Singh. Curcumin enhances the efficacy of docetaxel- induced apoptosis of prostate cancer cell. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3841.

Gluten is the most abundant storage protein of wheat representing about 80 % of the total grain proteins and is composed of gliadins and glutenins. Glutenins are composed of high molecular weight (HMW) and low molecular weight (LMW) glutenin subunits which can be detected by SDS-PAGE. HMWGS are coded by three different loci namely Glu-A1, Glu-B1 and Glu-D1 . Allelic diversity of protein subunits at these three loci was used to study the genetic relatedness of 35 bread wheat genotypes and their effect on bread making quality. Clustering of the genotypes revealed institutional, zonal and temporal prevalence of particular subunit combinations in the varieties. A novel HMW glutenin subunit designated as ‘17*’ reported earlier was confirmed in the land race Pissi-local. Allelic variation at the Glu-D1 locus was found to be an important determinant of bread making quality and allele of Glu-D1 encoding the subunits ‘5 + 10’ was superior to its allelic counterpart, encoding ‘2 + 12’. One new subunit ‘12 2 ’ (coded by Glu-D1-2 ) earlier reported in Indian cultivar C 306 was found to be present in three more varieties with similar parentage. Effect of this subunit relative to the ‘2 + 12’ subunit on bread making quality is reported in this study. The effect of allelic variation at Glu-A1 and Glu-B1 loci on the loaf volume was dependent on the alleles present at the Glu-D1 locus. Epistatic effect among the three ‘ Glu- 1’ loci was detected with respect to bread loaf volume.

Genetic diversity among 35 wheat cultivars was evaluated using 30 polymorphic microsatellite (SSR) markers. Analysis of molecular diversity revealed moderate levels of polymorphism in the set of genotypes studied. Ninety alleles with an average of three alleles per locus were detected. The allelic polymorphism information content (PIC) value ranged from 0.06 to 0.76 with an average of 0.45. The primers like Xgwm294, Xgwm146, Xgwm455, Xgwm497, Xgwm136 and Xgwm132 could be considered particularly informative, as they revealed four or more alleles per locus and displayed high PIC values.Ten rare and three unique alleles were recorded. The most closely related cultivars were ‘Raj3765’ and ‘HD 2402’ displaying the lowest dissimilarity index, whereas highest genetic distance was observed between ‘Pissi Local’ and ‘HB 208’.The land race ‘Pissi Local’ revealed very high genetic distance with most of the cultivars where the dissimilarity indices ranged from 0.42–0.74. Three major clusters comprising 13, 12 and 10 genotypes were formed. Despite the presence of variability among the different Indian cultivars the varieties developed at various institutes during different time periods clustered together indicating the use of common genotypes in the pedigree.