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Self-assembled peptide fibrils have been used extensively to template the organization of metal nanoparticles in a one-dimensional (1D) array. It has been observed that the formation of the 1D arrays with a width of a single or few nanoparticles (viz. 20 nm diameter) is only possible if the templating fibers have comparable diameters (viz. ≤20 nm). Accordingly, until today, all the peptide-based templates enabling such 1D arrays have very low persistence lengths, a property that depends strongly on the diameter of the template, owing to the inherent flexibility of only a few nanometer-wide fibers. Here, we demonstrate the formation of high persistence length 1D arrays templated by a short self-assembling peptide fibril with an asymmetrically distributed charged surface. The asymmetric nature of the peptide fibril allows charge-dependent deposition of the nanoparticles only to the part of the fiber with complementary charges, and the rest of the fibril surface remains free of nanoparticles. Consequently, fibers with a much higher diameter, which will have a higher persistence length, are able to template single or few nanoparticle-wide 1D arrays. Detailed microscopy, molecular dynamics simulations, and crystal structure analysis provide molecular-level insights into fiber asymmetry and its interactions with diverse nanostructures such as gold and magnetic nanoparticles. This study will afford an alternative paradigm for high persistence length 1D array fabrication comparable to DNA nanotechnology and lithography but with tremendous cost-effectiveness.

KRAS and BRAF are key proto-oncogenes of MAPK/ERK pathway and are essential for cell growth and proliferation. Mutations of these oncogenes are known to have role in pathogenesis of epithelial ovarian carcinoma (EOC). However, limited studies have evaluated the role of KRAS and BRAF protein expression. Hence, this study aimed to explore their role in EOC patients, specifically to correlate KRAS and BRAF protein expression with the histological subtypes and other histopathological prognostic factors. Immunohistochemistry was performed using paraffin-embedded tumor tissue blocks of 55 untreated and histologically confirmed EOC patients and 20 benign ovarian tumors to study KRAS and BRAF protein expression. Data were analyzed using SPSS software. Cytoplasmic expression of both KRAS and BRAF was observed in EOC and benign tumors. KRAS protein expression was significantly higher in serous EOC patients than the mucinous EOC patients (P = 0.016). KRAS expression was also significantly positively correlated with the presence of lymphatic permeation (P = 0.030), while a trend toward significance was found with vascular permeation (P = 0.052). Furthermore, BRAF protein expression was significantly higher in EOC patients than in benign ovarian tumors (P = 0.027). Its expression was significantly higher in patients with moderately/poorly differentiated tumors than well-differentiated tumors (P = 0.008), and in patients having serous EOC than in mucinous EOC (P = 0.001). A trend of higher BRAF expression was also observed in patients with lymphnode metastasis (P = 0.079). KRAS and BRAF proteins have a potential role in EOCs. However, further studies in larger group of patients and follow-up for a longer period are required to identify their role in prognosis.

This paper looks at the paradoxes represented by Tamil author Bama and her writing. As a lower caste Christian, Bama writes her stories in English, the language of the pan-Indian urban middle class. In seeking a wider audience, Bama wishes to choose for herself the identity of an English-speaking writer and intellectual who is also a part of India’s cosmopolitan, secular culture associated with late modernity. In so doing she seeks to escape to an extent the fixity of her regional, ethnic, caste identity while creating alternative spaces where she can imagine other identities. This is in contrast to the tensions represented in the discourses, articulated by scholars like GN Devy, on translating local, regional, and tribal languages and literatures into English where the gaining of a wider audience is accompanied by the loss of alternative, pluralistic literary traditions that cannot really be articulated outside of their languages. This paper reads these debates within a context of ongoing discussions in the media in the last three decades of the 20th century about gendered minority cultures and their difficulties in belonging to a national community.

Nanomaterials have potential biomedical application such as imaging, targeted drug delivery, disease diagnosis, disease prevention, and controlled dug release. Some nanoparticles such as guar gum nanoparticles (GN) itself show anti-inflammatory and proregenerative properties, while others such as mesoporous carbon nanoparticles (MCN) act as potent delivery agents to fight inflammatory diseases. The graphene oxide (GO) nanoparticles on the other hand are cost-effective and widely used for catalysis and drug delivery purposes. The fluorescent tagging of nanoparticles helps in monitoring the biodistribution and retention through imaging. The drug release is quantified by the release kinetics of nanoparticles and is dependent on the pH, biomaterial, electric field, magnetic field, and the route of administration. The diagnostic applications include imaging and use of biosensors in the field of biomedicines. Use of nanomaterials as dental adhesives and nanomaterials with DNA vaccine has been widely used for the disease prevention. The engineering of nanoparticle surfaces and their associated pharmacokinetics helps in the formation of immune safe biomedicine.

Tissue engineering involves restoration of altered tissue architecture by transplantation of cells on supportive matrix formed by scaffolds and nanoscaffolds. The matrix fabrication provides 3D platform for suitable cellular interaction for performing biochemical functions. The matrix supports the cellular growth by cell adhesion, migration, proliferation, differentiation followed by colonization of cells onto it. The nanoscale fabrication of scaffolds resembles the structural features of extracellular matrix (ECM). The cells colonized on nanoscaffolds are biocompatible, immunocompatible, and biofunctional tissue inside the body, thus eliminating the chance of rejection. The cellular implantation using scaffolds on skin tissue may help to combat the drawbacks which are associated with the autologous grafting and allograft tissue transplantation. The nanoscaffolds play a potent role in combating the bone and cartilage defects. The scaffold formed by the combination of organic and inorganic particle showed improved biocompatibility and mechanical strength in bone tissue engineering

Introduction: Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish and scaly lesions. It mainly affects children and has a high prevalence in developing countries. AD may occur due to environmental or genetic factors. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by macrophages. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in AD. Methods: To assess the wound healing capacity of GN, we first treated adherent fibroblast cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiments, Balb/c mice ears were treated topically with oxazolone (Oxa) to induce AD, and then were topically treated with GN. The ear thickness increased significantly until day 28 upon treatment with Oxa. Results: Application of GN showed a significant decrease in ear thickness as assessed on day 28. The total cell count of skin cells that showed a fold increase, when treated with Oxa, was again decreased after topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining, was also increased when treated with Oxa, while GN application led to a significant decrease. Serum IgE levels were restored by GN. T helper cell and macrophage populations, when examined by flow cytometry, showed an increase in percentage when treated with Oxa; the percentage was reduced after application of GN. Hematoxylin & Eosin (H&E) staining of the ear tissue showed an increase in epidermal thickness in Oxa-treated mice, while GN application showed reduced cellular infiltration and epidermal thickness. Conclusion: Overall, our results showed that GN, when administered topically, was successful in alleviating dermatitis caused by Oxa.

Aim: The aim of this study is to analyze the protein expression of interleukin 18 (IL-18) in patients with untreated breast cancer and further to evaluate its clinical efficacy in predicting treatment outcome. Methods: In the present study, a total of 50 untreated patients with invasive ductal carcinoma of breast were included in the study. Expression of IL-18 was studied by immunohistochemistry method. Statistical analysis was carried out using Statistical Package for Social Sciences statistical software and P ≤ 0.05 was considered statistically significant. Results: Seventy-two percent of the breast cancer patients showed the presence of cytoplasmic and/or nuclear IL-18 immunoreactivity. IL-18 expression was significantly and positively correlated with the stromal response (χ2 = 3.97, r = 0.282, P = 0.044). Further, the IL-18 immunoreactivity was significantly higher in patients with HER2 amplification as compared to luminal B (χ2 = 2.82, r = −0.523, P = 0.047) breast cancer patients. Moreover, a trend of increased IL-18 expression was observed in estrogen/progesterone receptor (ER/PR) negative patients as compared to ER/PR positive patients (χ2 = 3.41, r = −0.282, P = 0.066). Conclusion: IL-18 could be used as a potential predictive marker and guide clinicians for recommendations to newer treatment. It might serve as a potential therapeutic target to establish novel treatment approaches along with the current treatment protocol used.

Purpose: Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer. Materials and Methods: SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software. Results: Expressions of SOCS proteins were significantly higher in papillary thyroid cancer than in patients having benign disease. SOCS-1 expression was predominantly higher in males (P = 0.004), unilateral tumors (P = 0.030), and noninflammatory conditions (P = 0.028). SOCS-1 expression was also able to predict poor overall survival in subgroup of papillary thyroid cancer patients having larger tumor size (P = 0.013) and advanced stage disease (P = 0.033). Expression of SOCS-2 significantly correlated with tumor size (P = 0.017), extrathyroidal extension (P = 0.000), residual disease (P = 0.043), and treatment (P = 0.007), while preponderance of SOCS-3 expression was observed in males (P = 0.030) and in patients having extrathyroidal extension (P = 0.011) and absence of metastasis (P = 0.032). Conclusion: Expression of the studied SOCS proteins may be a consequence of activation of Janus kinase-signal transducers and activators of transcription and other pathways supporting growth and survival of cancer cells that are sustained by several cytokines. Thus, SOCS-1, SOCS-2, and SOCS-3 proteins may directly or indirectly, have important roles in development and pathogenesis of papillary thyroid cancer.

Cancer development and progression as well as tumor recurrence are largely due to the presence of cancer stem cells (CSCs) that are maintained through various pathways. Wnt/β-catenin signaling is the fundamental pathway, which when deregulated leads to tumor development by sustaining CSC population. Along with the upregulation of its various components, Wnt pathway is highly active in cancer cells resulting in increased expression of the target genes. In breast cancer condition, convincing results are available wherein the Wnt pathway activation in breast cancer cells increases the cell motility while its blockade suppresses their aggressive behavior in vitro. Further, numerous reports on breast cancer patients have documented the importance of activation of Wnt pathway and its components to an extent that the regulation can be exploited therapeutically with promising results. In addition, recent research has laid emphasis on the significance of Wnt pathway in the triple-negative breast cancer, a molecular subtype of breast cancer, which lacks targeted therapy till date. Hence, understanding of Wnt signaling and its targeting to treat such patients can be an assuring approach.

Circulating levels of TNF-αand the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-αand L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-αand L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-αlevels significantly positively correlated with the levels of L-Selectin, while TNF-αimmunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-αwas found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-αand the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer.

Introduction: 5-flourouracil (5-FU) is one of the standard chemotherapeutic drugs used today in the treatment of colorectal cancer patients. Disruption of 5-FU metabolic pathway may contribute to altered effectiveness towards 5-FU-based therapy. Hence, the study of 5-FU metabolizing enzymes might have the potential efficacy to predict survival and response to treatment in colorectal cancer patients. Materials and methods: Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated. Results: Immuno-positivity for TS, MTHFR, DPYD, and TP was observed in 77%, 75%, 88%, and 96% of colorectal cancer patients, respectively. Univariate survival analysis in total patients showed that low DPYD expression significantly predicted adverse overall survival ( P=0.042). Moreover, subgroup of colon cancer patients with low TS expression was associated with unfavorable prognosis. TP expression also emerged as a prognosticator in the subgroup of early and advanced stage patients. Additionally, when effect of co-expression of 5-FU metabolic enzymes was evaluated in total patients, low coexpression of all four proteins was predictive of poor overall survival than for individuals expressing high coexpression of these proteins ( P=0.045). In contrast, none of the 5-FU metabolic enzymes—either singly or on coexpression—emerged as a useful biomarker of potential therapeutic value when evaluated in the subgroup of patients treated with 5-FU alone or 5-FU plus oxaliplatin. Conclusion: The above findings suggest that coexpression of 5-FU metabolic enzymes possess significant prognostic value and could be useful biomarkers in colorectal cancer patients.

Using the idea of a border as a method, this chapter examines three late twentieth- to early twenty-first-century literary and news stories that narrate the ‘New Woman’ as a signifier that destabilizes established meanings of femininity within India. Gulnari (Partap Sharma’s Days of the Turban, 1986) breaks codes of respectability when she joins the Akali movement as a revolutionary and interacts with men of different castes and faiths. Akhila (Anita Nair’s Ladies Coupѐ, 2001), a 45-year-old income-tax clerk, breaks conservative Tamilian Brahmanical norms governing her behaviour when she decides to explore if a woman can live feasibly without marriage. In news stories of the Park Street rape case (2012), Suzette Jordan—a single, working mother—challenged a number of norms when she was gang raped: her right to be out late, to accept drinks at a bar, and get a ride home without being raped. These women’s choices serve as flashpoints within a nation, problematizing its self-definition as modern.

Background The mediator of DNA damage checkpoint protein 1 (MDC1) is involved in the regulation of cell cycle checkpoints and recruitment of several repair proteins to the site of DNA double-stranded breaks (DSBs). This study aimed to correlate the expression of MDC1 protein with clinicopathological parameters and to evaluate its prognostic significance in patients with oral squamous cell carcinoma (OSCC). Methods MDC1 protein expression was evaluated immunohistochemically from untreated 100 patients with OSCC using modified H-score method. The association of MDC1 immunostaining was evaluated with clinicopathological parameters and disease outcome using univariate and multivariate survival analysis for relapse-free survival (RFS) and overall survival (OS). Results Incidence of nuclear and cytoplasmic expression of MDC1 protein was 85% & 92%, respectively. Strong nuclear MDC1 protein expression was found to be significantly correlated with lymph node metastasis (P = 0.032). For RFS, Kaplan–Meier survival analysis demonstrated that presence of metastatic lymph node (P = 0.001), lymphatic permeation (P = 0.020), and nuclear MDC1 (P = 0.005) remained significant risk predictors. In multivariate survival analysis, nuclear MDC1 (P = 0.027) entered at step 2 after presence of metastatic lymph node (P = 0.002) at step 1 for predicting reduced RFS. In relation to treatment, OSCC patients exhibiting weak expression of nuclear MDC1 protein were benefited significantly when treated with surgery followed by radiation therapy (P = 0.001). Conclusion Thus, this study showed that MDC1 protein expression could be used as a prognostic marker in predicting relapse-free survival in patients with OSCC. OSCC patients expressing weak MDC1 protein could be benefited by adjuvant radiotherapy instead chemo-radiotherapy.

Introduction: Wnt signaling pathway is often dysregulated in the pathogenesis of various malignancies, including breast cancer. This might be related to methylation of the genes encoding antagonists of this signaling pathway. Aim: The aim of the study was to analyze the methylation status of the promoter regions of Wnt antagonists-secreted frizzled-related protein 1 (sFRP1) and Dickkopf 3 (DKK3) and to determine their correlation with clinicopathological parameters and survival outcome in patients with primary invasive ductal breast cancer. Materials and Methods: The methylation status of sFRP1 and DKK3 was analyzed in 160 breast tumor samples using methylation-specific polymerase chain reaction. Statistical analysis was performed using SPSS software. P ≤ 0.05 was considered as statistically significant. Results: The promoter region of sFRP1 and DKK3 genes was found to be methylated in 76% and 64% of total invasive ductal breast cancer patients, respectively. The promoter methylation in sFRP1 and DKK3 genes was significantly associated with larger tumor size, positive lymph nodes, advanced stage, and perinodal extension of breast tumors. Further, sFRP1 methylation was associated with human epidermal growth factor receptor 2-positive tumors while DKK3 methylation was associated with Grade 3 tumors. Survival analysis demonstrated that sFRP1 methylation was correlated with reduced overall survival in breast cancer patients. Conclusion: Promoter methylation of Wnt pathway antagonists is frequent in breast cancer ultimately leading to probable upregulation of the pathway in these tumors. Hence, sFRP1 and DKK3 methylation may be used as a valuable biomarker in clinical breast cancer management.

This article focuses on the complex interplay between the migrancy of laboring bodies in the informal sectors of various economies, the spaces they inhabit, and the gendered experiences of their lives. It does so by comparing two literary works that present various forms of narratives: Borderlands/La Frontera: The New Mestiza by Chicana writer Gloria Anzaldua and The White Tiger by Indian novelist Aravind Adiga. Both works present powerful images of gendered rural migrants who travel to cosmopolitan locations where their labor is consumed and erased. La Frontera deals with Chicana characters who cross over from Mexico to the U.S. in search of daily wage-based work. The White Tiger focuses on Balram Halwai, a taxi driver, who travels between rural and urban India. Thus, in using literary narratives, this article seeks to understand how these stage the commoditization and erasure of labor in its production of space even as these texts undergo their own processes of production, consumption, and commoditization in global circuits of exchange.

In my introduction, I seek to provide a theoretical framework for reading the critical essays, narratives and poetry depicting women's struggles over water. I use theories about capital accumulation, the commodification of natural resources and women's bodies, biopolitical state power, the state of exception, the bare life and the new imperialism. I believe that these theories illustrate the multiple yet specific ways in which the gendered politics of water plays out in different contexts. I invite readers to understand this layered perspective in relation to another kind of layering – the intertexual generic expectations that get built into the act of reading the various kinds of texts included in this issue.

An efficient synthetic approach to the core structure of the manzamine alkaloids is reported, particularly in relation to incorporating a one-carbon unit in ring B from which the aldehyde in ircinal A or the beta-carboline unit in manzamine A could potentially be generated. The key steps involve a Johnson–Claisen rearrangement, enolate alkylation, dithiane alkylation and a stereoselective intramolecular dipolar cycloaddition of an azomethine ylide, which provided the desired tricyclic ABC core structure.

(2005). (Re)Writing History, (Un)Settling Relationships: The Indian National Imaginary and Alternate Maps of Belonging. South Asian Review: Vol. 26, No. 2, pp. 96-115.

In fluorescence quenching study via electron transfer (ET), the quenching rate constant ( k q ) values generally decrease with lowering of quencher concentration, since smaller concentration of quencher always leads to a red shift in the donor–acceptor (D–A) distance in ET [M. Tachiya, S. Murata, J. Phys. Chem. 96 (1992) 8441; S. Murata, M. Tachiya, J. Phys. Chem. 100 (1996) 4064; L. Burel, M. Mastafavi, S. Murata, M. Tachiya, J. Phys. Chem. A 103 (1999) 5882]. However, while doing a comparative study with different carbazole (CZ) derivatives–1,4-dicyanobenzene (DCB) systems in benzene (BZ), we observed a deviation from that normal behaviour. It was found that for all of them with lower quencher (DCB) concentration, k q values actually increase instead of the expected reduction. Exceptionally, for simple CZ (C 12 H 9 N) with decrease in concentration of DCB, k q values can even reach the order of energy transfer (10 11 s −1 ). Interestingly, it is not observed when toluene (TL) or xylene (XY) is used as solvent. To explain this unique observation, a sandwich type of molecular structure is predicted, where BZ sliding in between CZ and DCB brings them closer enough, imparting more through bond character to CZ–DCB interaction and hence a higher rate of ET ( k q ) is observed [L. Burel, M. Mastafavi, S. Murata, M. Tachiya, J. Phys. Chem. A. 103 (1999) 5882].

A simple and efficient synthesis of bis(indolyl)ethylamines and three bisindolic natural products, viz. hallucinogenic 6, genotoxic 7 and the alkanoic acid 8 has been developed by the reaction of indoles with appropriate carbonyl compounds on montmorillonite K10 clay.

We did a comparative fluorescence quenching study with different derivatives of carbazole (CZ) as fluorophore and 1,4-dicyanobenzene (DCB) as quencher. It was found that the bimolecular fluorescence quenching rate constant (kq) values in N,N-dimethylformamide (DMF) were almost half of that reported for a much less polar solvent tetra-hydrofuran (THF), which is something exceptional. Moreover, this phenomenon was not system specific. Similar results were obtained for some other systems too. In this communication while trying to resolve this unique problem, we have found that micro heterogeneous nature of DMF, its high viscosity and certain impurities present in the commercial grade of this solvent are probably responsible for such anomalous result.

Michael reaction of 3-(2′-nitrovinyl)indole with eight 3-unsubstituted indoles on TLC-grade silica gel furnished unsymmetrical bis(indolyl)nitroethanes in 7–12 min under microwave irradiation and in 8–14 h at rt. In contrast, the p -TsOH-catalysed reaction of the nitrovinylindole with the 3-unsubstituted and two 3-substituted indoles in solution under reflux furnished both unsymmetrical and symmetrical bis(indolyl)nitroethanes, the latter resulting from novel tandem Michael addition–elimination–Michael addition reactions. The synthesis of a 2′,3″-bis(indolyl)nitroethane, the precursor core structure of two bioactive marine metabolites, and the reduction of 2,2-bis(3′-indolyl)nitroethane to the corresponding ethylamine, isolated as its N -acetyl derivative, have been achieved. Significantly, attempted hydrolysis of three nitronates, derived from the corresponding bis(indolyl)nitroethanes, with buffered aqueous TiCl 3 has led to the first isolation of oximes ( syn / anti -mixture) as the only products.

Dry reaction of indoles 1a – c with aldehydes 2a – i , ketones 2j – o and an acetal 2p on M. K10 clay at room temperature furnished 3,3′-diindolylalkanes (DIAs: 3a – h , j – r ). The novel formation of tris(3-indolyl)methane 4 from 2i through tandem reactions and of the DIAs 6 and 8 from 1d through Plancher rearrangements were also observed.

1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was found to smoothly cleave the N-acetyl and N-benzoyl derivatives of carbazoles, indoles and nitroanilines quickly in refluxing methanol and the parent amines were recovered in excellent yields. Complete cleavage could also be accomplished in acetonitrile solution under reflux and also under microwave irradiation, which, however, required considerably longer periods.

The purpose of this study was to examine the association of telomerase activity with clinical and histopathological prognostic variables in primary breast cancer (n=64). Telomerase activity in breast cancer was also compared with that in benign (n=10) and non-malignant tissues (n=8; post-lumpectomy tissues histopathologically defined as containing no residual tumor). The parameter was assessed using the Telomerase PCR ELISA kit. Values above OD 0.120 were considered positive. Estrogen and progesterone receptors (ER and PgR) were assayed by the dextran-coated charcoal method and levels >10 fmol/mg cytosol protein were taken as positive. Telomerase activity was detected in 20% and 50% of the patients with benign lesions and primary breast cancer, respectively, and in 50% of post-lumpectomy breast tissues histopathologically defined as containing no residual tumor. Telomerase activity was present in all stages of breast carcinoma and showed a significant inverse correlation with lymph node status (p=0.006), lymphatic invasion (p=0.035) and necrosis (p=0.033). Moreover, when stage II patients were grouped according to nodal involvement, a trend towards significance was observed (p=0.055). No correlation was observed with ER and PgR. The results of our study suggest that telomerase activity might be associated with the presence of cancer cells. Furthermore, telomerase activation may occur early in breast cancer and may be periodically downregulated during subsequent tumor progression.

Background: Thymidylate synthase (TS) plays a critical role in nucleotide metabolism and is an important target for 5-fluorouracil (5-FU), the standard chemotherapeutic drug for treatment of colorectal cancer (CRC). Aims and Methods: The present study aimed to evaluate TS variable number tandem repeat sequences (VNTR) polymorphism by polymerase chain reaction and TS protein expression by immunohistochemistry and its association with clinicopathological parameters in untreated CRC patients (n = 100). Further, the prognostic and predictive role of TS has been evaluated. Results: For TS VNTR polymorphism, the observed frequencies of 2R/2R, 2R/3R, and 3R/3R genotypes were 22%, 51%, and 27%, respectively. When immunohistochemical localization was studied, cytoplasmic staining for TS was observed in 70% of patients. A significant inverse correlation was noted between TS protein expression and tumor, node, metastasis staging (P = 0.027), Dukes' staging (P = 0.039), and lymph node status (P = 0.012) of CRC patients. However, there was no significant correlation between TS VNTR polymorphism and TS protein expression. On survival analysis, a significantly shorter overall survival (OS) was seen in CRC patients with negative protein expression (P = 0.031). Moreover, the subgroup of CRC patients treated only with surgery also showed a trend of poor OS in patients with negative TS protein expression (P = 0.058). However, neither TS polymorphism nor its protein expression was able to predict relapse-free survival. Conclusion: Negative TS protein expression may be related to unfavorable clinical outcome in CRC patients. However, further studies in a larger set of patients are necessary to better assess TS as a prognostic and predictive marker for 5-FU response in CRC patients.

Background: The aim was to investigate the expression of a panel of biomarkers such as prolactin (PRL), p53, Bcl-2, c-erb B2, Ki-67, CD44, and factor VIII-related antigen (FVIII-RA) in primary tumors of stage II and stage III breast cancer and its correlation with disease prognostication. Methods: The streptavidin-biotin peroxidase complex technique was used for the detection of these antigens. Cytoplasmic staining pattern was observed for PRL, Bcl-2, and Ki-67. Staining pattern for p53 was nuclear. Membranous and/or cytoplasmic staining was noted for c-erb B2 and CD44. Microvessel staining was noted for FVIII-RA. Results: Of the 93 primary breast tumors analyzed, positivity for PRL was noted in 82%, for p53 in 56%, for Bcl-2 in 73%, for c-erb B2 in 68%, and for Ki-67 and CD44 in 78% each. The microvessel count (MVC) for FVIII-RA ranged from 0.0 to 29.0, with a median of 6.0, which was used as a cutoff. MVC $ 6.0 was noted in 51% of breast tumors. With increasing tumor size, the higher frequency of positivity of MVC $ 6.0 (P 5 .0001), CD44 (P 5 .001), PRL (P 5 .002), and c-erb B2 (P 5 .008), and higher frequency of Bcl-2 negativity (P 5 .033), was noted. In stage III patients, a higher positivity of the following biomarkers was noted, compared with stage II patients: MVC $ 6.0 (P 5 .0004), PRL (P 5 .0002), c-erb B2 (P 5 .001), and CD44 (P 5 .005). Further, Bcl-2 positivity was significantly lower in patients with stage III disease compared with those with stage II disease (P 5 .024). In patients with nodal involvement, the frequency of c-erb B2 (P 5 .006), MVC $ 6.0 (P 5 .011), and PRL (P 5 .032) was higher than in those without nodal involvement. Moreover, in these patients, with the increase in the number of involved lymph nodes, there was a significant increase in frequency of CD441 (P 5 .0004) and PRL1 (P 5 .013) tumors. Abnormal expression of one biomarker was seen in 7% of tumors, of two biomarkers in 4%, of three in 15%, of four in 19%, of five in 28%, of six in 20%, and of all seven biomarkers in 7% of tumors. The frequency of an increasing number of biomarkers coexpressed was higher in stage III patients compared with stage II patients (P 5 .00003). In the total number of patients (n 5 93), tumors with Bcl-2 negativity (P 5 .00001), MVC $ 6.0 (P 5 .001), PRL positivity (P 5 .02), and CD44 positivity (P 5 .034) had a significantly poorer overall survival (OS) compared with their respective counterparts. In stage II patients (n 5 40), only p53 expression was significantly associated with reduced relapse-free survival (P 5 .009) and OS (P 5 .040). In multivariate analysis, p53 expression was an independent prognostic factor that influenced relapse-free survival (P 5 .034) of stage II breast cancer patients. However, it failed to attain statistical significance for OS. In stage III patients (n 5 53), tumors with Bcl-2 negativity (P 5 .0005) and MVC $ 6.0 (P 5 .039) had a significantly poorer OS compared with their respective counterparts. In multivariate analysis of stage III patients, Bcl-2 was the only independent prognostic factor (P 5 .001) for predicting OS. There was a significant association between coexpression of the biomarkers and OS (P 5 .001). The OS rates decreased with the increase in number of abnormally expressed biomarkers. Conclusions: p53 expression in primary tumors was an independent prognostic factor that influenced relapse-free survival in patients with stage II disease. In stage III patients, lack of Bcl-2 expression was independently associated with a poor prognosis and, thus, may be an indicator of aggressive phenotype.

Background The purpose of this study was to assess the role of prolactin (PRL) in men with locally advanced tongue cancer. Methods Circulating PRL was assayed immunoradiometrically in pretherapeutic and sequential blood samples of 99 patients with locally advanced tongue cancer. Patients were followed for 3 years or until their death within a stipulated time. Immunohistochemical localization of PRL was performed on formalin-fixed paraffin-embedded tissue sections. Tumoral prolactin receptors (PRLR) were estimated by ligand binding assay; the expression of PRL mRNA and PRLR mRNA were carried out by reverse transcriptase polymerase chain reaction (RT-PCR). Furthermore, PRL amplimer was sequenced and compared with human pituitary PRL amplimer. Results Pretherapeutic PRL levels were significantly higher in patients with locally advanced tongue cancer compared with controls (p = .01). Thirty-four percent (34 of 99) of the patients had hyperprolactinemia (PRL ≥15.0 ng/mL). Univariate survival analysis showed that patients with pretherapeutic hyperprolactinemia had a significantly shorter overall survival than patients with pretherapeutic PRL

The goal was to investigate the potential correlation between overexpression of CD44, high microvessel count (MVC), and p21ras with length of relapse-free and overall survival in patients with colorectal adenocarcinomas.CD44, factor VIII-related antigen (FVIII-RA), and p21ras were localized immunohistochemically in patients with colorectal adenomatous polyps (n = 8) and adenocarcinomas (n = 98). The correlation between the expression of CD44, MVC in the areas with highest density, and p21ras with relapse-free and overall survival time was investigated. Data were analyzed statistically using univariate and multivariate systems.In patients with adenomatous polyps, the positivity of CD44, FVIII-RA, and p21ras was 75%, 62%, and 88%, respectively. In patients with colorectal carcinomas the positivity of CD44 was 55%, and for p21ras it was 52%. The median of FVIII-RA was 4 MVC (range, 0.0 to 32.33). MVC was greater than 4 in 53% of the patients with colorectal carcinomas. In univariate analysis, a significantly longer relapse-free time (CD44: P = .0004; FVIII-RA: P = .0006) and overall survival time (CD44: P = .0001; FVIII-RA: P = .001) were observed for patients with CD44-negative tumors and MVC below 4 as compared to those with CD44-positive tumors and MVC greater than 4. Similar observations were noted in patients with Dukes B and C disease and the rectum as the site of tumor. In multivariate analysis, only CD44 correlated significantly with both relapse-free (P = .0003) and overall survival (P = .00001).Univariate analysis showed CD44 and MVC to be independent predictors of prognosis in colorectal carcinomas. Multivariate analysis showed that CD44 positivity was the most important indicator of an unfavorable prognosis for relapse-free and overall survival in patients with colorectal cancer. Thus, it can be deduced that whether CD44 is positive or negative in patients with colorectal cancer may have prognostic importance and in the future may be used as a factor in the pathologic evaluation of tumor specimens. This hypothesis needs to be tested prospectively in a larger number of patients.

Background and Objective The purpose of this retrospective study was to test whether the expression of p53, nm23, and bcl-2 in T3–4N1M0 oesophageal carcinoma is associated with patient survival. Methods Immunohistochemical localisation of p53, nm23, and bcl-2 was performed on formalin-fixed, paraffin-embedded tissue sections (N = 46). The observed range of follow-up period was 0.2–24.0 months with a median of 11.0 months. A total of 85% (39/46) of the patients died within 24.0 months, which could be due to advanced disease at presentation. The immunohistochemical signal was expressed as the proportion of positive cells. The immunostaining for p53 was nuclear, whereas that for nm23 and bcl-2 was cytoplasmic in the neoplastic cells. Results p53 was expressed in 70% (32/46) of cases; nm23 in 29% (13/45), and bcl-2 in 67% (29/43) of tumours. The univariate analysis showed that the expression of two markers, i.e., expression of p53 and absence of nm23 were independently associated with unfavourable overall survival time. Despite a small number of patients treated with adjuvant therapy, we observed that tumours positive for p53 had an unfavourable prognosis when compared with tumours negative for p53. Conclusions Our preliminary findings suggest: expression of p53 and nm23 negativity may be related to an unfavourable prognosis in patients with advanced oesophageal carcinoma. J. Surg. Oncol. 1997;65:111–116. © 1997 Wiley-Liss, Inc.

In this communication we have reported the steric effect on the fluorescence quenching rate constants of the electron transfer (ET) process. We have done a comparative study using donor (D)-acceptor (A) systems with different exergonicity (-deltaG(f)). Different carbazole derivatives (CZ): 1,4-dicyanobenzene (DCB) systems (-deltaG(f) = 0.7-0.8 eV) were found to be among those limiting systems that show a clear-cut steric dominance in the process of fluorescence quenching. It is known that with increasing exergonicity the ET distance increases and hence steric dependence becomes insignificant. On the other hand, with decreasing exergonicity the ET distance decreases and a pronounced steric dominance should be observed. However, in the D-A systems having lower exergonicity compared to CZ-DCB systems, this steric dominance is observed only in polar medium. In non-polar medium due to exciplex formation the D-A distance effectively becomes much longer and therefore no steric dominance is observed.

The purpose of this study was to investigate a prognostic indicator that can differentiate node negative breast cancer patients (N = 39, T2N0M0) with high risk and low risk for the development of recurrence or metastases. Preoperative plasma prolactin (PRL) was estimated by radioimmunoassay. The expression of PRL, p53, nm23, and c-erbB2 was investigated by immunohistochemical (IHC) localization; cathepsin D (CD, Enzyme Linked Sorbant Assay) and estrogen- and progesterone-receptors (ER and PR, Dextran coated charcoal method) were estimated in the tumor cytosols. The follow-up period was 2-6 years. Statistical comparisons were made between each marker for relapse-free survival (RFS) and overall survival (OS). Of the 39 patients, 18 had hyperprolactinemia (PRL > 20.0 ng/ml plasma), whereas overexpression of p53 was observed in 55% (17/31) tumors. These were independently and in combination associated with a reduced RFS and OS. The rest of the investigated markers did not show promising results. Hyperprolactinemia and/or overexpression of p53 were associated with aggressiveness of the tumor, early disease relapse or metastases, and poor OS in patients with node negative breast cancer. These two markers may enhance our ability to identify node negative breast cancer patients with aggressive tumors, for whom the use of adjuvant chemo and/or endocrine therapy is unequivocally justified.

The 3-aminocarbazoles 1a – e were condensed with phenyl and benzyl isothiocyanates on montmorillonite K10 clay or TLC-grade silica gel at room temperature to furnish efficiently the N -phenyl and N -benzylthioureidocarbazoles, 2a – e and 2f , respectively, within minutes. When adsorbed on montmorillonite K10 clay impregnated with para -toluene sulfonic acid (1:1, w/w) and heated at 60–70 °C, 2a – e and 2f furnished the 2-anilino and 2-benzylaminothiazolo[4,5- c ]carbazoles, 3a – e and 3f , respectively, regioselectively in high yields. The cyclisation was also effective for the N -methylthioureidocarbazoles 2g – i .

Primary ciliary dyskinesia (PCD) is an autosomal recessive heterogeneous group of conditions with variable clinical findings like recurrent respiratory tract infections, bronchiectasis, situs inversus, singly or in various combinations. Development of Pulmonary arterial hypertension can be a late complication of this disease. Here we present a case of PCD with recurrent respiratory tract infections, bronchiectasis and severe PAH, who responded to treatment with Oxygen, IV broad spectrum antibiotics and oral sildenafil.

Serum prolactin was measured pretherapeutically and sequentially thereafter using immunoradiometric assay method in 37 male patients with advanced tongue cancer and compared with 23 healthy, age-matched controls. Prolactin levels were correlated with age, various clinicopathologic parameters, overall survival, and patients with response and those with progressive disease. Patients with advanced tongue cancer had higher prolactin levels than controls (P0.02), but intergroup variation in prolactin was not observed when considering the age, site of the lesion, disease stage, histologic grade, and keratin. Of the patients, 30% had hyperprolactinemia (prolactin15.0 ng/ml). To assess the prognostic significance of pretherapeutic prolactin level, the patients were divided according to the cutoff level of prolactin (15.0 ng/ml). Hyperprolactinemic patients had more unfavourable prognosis than patients with prolactin15.0 ng/ml (X2 = 2.91, df = 1, P0.0037). In monitoring disease course, patients who responded to treatments had decreased prolactin levels at the end of 18 months as compared to their pretherapeutic levels (P0.01). In patients who subsequently developed progressive disease within 18 months, prolactin levels reduced initially at response, whereas with disease progression, prolactin levels increased significantly (P0.05). The positive and negative predictive value of prolactin was 100%. Immunohistochemical localization confirmed the ectopic production of prolactin by tongue tumors. In conclusion, our data indicate that hyperprolactinemia may be an independent predictor of short-term prognosis; circulating prolactin may be used as a marker for monitoring disease course in patients with advanced tongue cancer, and prolactin is produced ectopically by tongue tumors.

The prolactin receptors (PRLR) were correlated with circulating prolactin and various clinicopathologic parameters to investigate its prognostic value in patients with colorectal cancer. The prolactin (by radioimmunoassay) and its receptors (by radioligand method) were estimated in a total of 71 male patients with colorectal cancer enrolled at the Gujarat Cancer and Research Institute, Ahmedabad. The patients were followed for a period of 3 years. We have observed that 51% colorectal tumors were PRLR+. Significant correlation was not observed between presence/absence of PRLR and clinicopathologic variables. Dukes' D patients were lost to follow-up after 2-3 months; therefore, the results of prognostic significance were analysed only in patients with Dukes' A, B, and C (N = 64). Statistically significant difference in overall survival was not observed when the patients were subgrouped according to the presence/absence of PRLR and according to the cutoff level (i.e., 2%). PRLR+ hyperprolactinemic (Prolactin > 20.0 ng/ml plasma) patients had better overall survival than that of patients with PRLR- hyperprolactinemia, although the difference was statistically nonsignificant. However, PRLR- hyperprolactinemia patients had a more unfavourable prognosis than that of their counterparts. A similar trend was observed in patients with Dukes' B and C disease. Our preliminary study suggests an unequivocal finding, that PRLR- with concomitant hyperprolactinemia probably characterises a subgroup of patients with aggressive colorectal cancer.