An Amphiphilic Cell-Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9.

The discovery of safe platforms that can circumvent the endocytic pathway is of great significance for biological therapeutics that are usually degraded during endocytosis. Here we show that a self-assembled and dynamic macrocycle can passively diffuse through the cell membrane and deliver a broad range of biologics, including proteins, CRISPR Cas9, and ssDNA, directly to the cytosol while retaining their bioactivity. Cell-penetrating macrocycle CPM can be easily prepared from the room temperature condensation of diketopyrrolopyrrole lactams with diamines. We attribute the high cellular permeability of CPM to its amphiphilic nature and chameleonic properties. It adopts conformations that partially bury polar groups and expose hydrophobic side chains, thus self-assembling into micellar-like structures. Its superior fluorescence makes CPM trackable inside cells where it follows the endomembrane system. CPM outperformed commercial reagents for biologics delivery and showed high RNA knockdown efficiency of CRISPR Cas9. We envisage that this macrocycle will be an ideal starting point to design and synthesize biomimetic macrocyclic tags that can readily facilitate the interaction and uptake of biomolecules and overcome endosomal digestion.

Supramolecular Interaction of Molecular Cage and ß-Galactosidase: Application in Enzymatic Inhibition, Drug Delivery and Antimicrobial Activity.

Enzyme inhibitors play a crucial role in diagnosis of a wide spectrum of diseases related to bacterial infections. We report here the effect of a water-soluble self-assembled PdII8 molecular cage towards ß-galactosidase enzyme activity. The molecular cage is composed of a tetrapyridyl donor (L) and cis-[(en)Pd(NO3 )2 ] (en=ethane-1,2-diamine) acceptor and it has a hydrophobic internal cavity. We have observed that the acceptor moiety mainly possesses the ability to inactivate the ß-galactosidase enzyme activity. Kinetic investigation revealed the mixed mode of inhibition. This inhibition strategy was extended to control the growth of methicillin-resistant Staphylococcus aureus. The internalization of the Pd(II) cage inside the bacteria was confirmed when bacterial solutions were incubated with curcumin loaded cage. The intrinsic green fluorescence of curcumin made the bacteria glow when put under an optical microscope. Furthermore, this curcumin loaded molecular cage shows an enhanced antibacterial activity. Thus, PdII8 molecular cage is quite attractive due to its dual role as enzyme inhibitor and drug carrier.

Coordination-Driven Self-Assembly of Discrete Molecular Nanotubular Architectures.

Two new M8L4 tetrafacial nanotubes (T1 and T3) of different lengths have been synthesized in water using ligands L1 and L2, respectively, with acceptor cis-[(dch)Pt(NO3)2] (M) using coordination-driven self-assembly [where dch is 1,2-diaminocyclohexane, L1 is 1,4-di(pyrimidin-5-yl)benzene, and L2 is 4,4'- di(pyrimidin-5-yl)-1,1'-biphenyl]. In addition to complex T1, a tetrahedral cage of composition [M12(L1)6] (T2) was also formed in the self-assembly reaction of ligand L1 with cis-[(dch)Pt(NO3)2]. The precise composition of the products (T1 and T2) in solution was confirmed by 1H NMR and ESI-MS. Pure tube T1 was separated out by a crystallization technique and fully characterized by 1H NMR and X-ray diffraction. Temperature- and concentration-dependent NMR studies indicated no equilibrium between T1 and T2 in the solution phase, and the proportion of T1 and T2 in the mixture depends on the temperature of the reaction. In contrast to ligand L1, the self-assembly of the longer ligand, L2, with cis-[(dch)Pt(NO3)2] gave only tetrafacial tube [M8(L2)4] (T3) without any tetrahedral cage.

A Discrete Self-Assembled Pd12 Triangular Orthobicupola Cage and its Use for Intramolecular Cycloaddition.

Water-soluble Pd12 L6 coordination cage TC-1 was synthesized by coordination-driven self-assembly of symmetrical tetrapyridyl donor L with 90° ditopic acceptor cis-[Pd(NO3 )2 (tmeda)] [tmeda=N,N,N',N'-tetramethylethane-1,2-diamine]. The Pd12 L6 coordination assembly is an uncommon example of a coordination cage having triangular orthobicupola-like geometry. It was characterized by multinuclear NMR spectroscopy, ESI-MS, and single-crystal X-ray diffraction. Self-assembly of a tetratopic donor with a cis-blocked 90° ditopic acceptor generally yields tri-/tetra-/hexagonal barrels or closed cubic cages. However, in the present case the donor and acceptor are arranged in an unusual fashion to generate an orthobicupola geometry in which two triangular cupola share a common irregular hexagonal face. The cage was used to perform intramolecular cycloaddition reactions of O-propargylated benzylidinebarbituric acid derivatives in nitromethane. Several penta-/tetracyclouracil derivatives were synthesized through cage-catalyzed [4+2] cycloaddition reactions in a concerted manner with good to high conversion under mild reaction conditions, whereas in the absence of cage TC-1 similar reactions led to lower conversion to the cyclized products in organic solvent. This approach is of particular importance compared to the literature reports on the synthesis of similar compounds under high-temperature reflux conditions with high catalyst loading.

Self-Assembly of Discrete RuII8 Molecular Cages and Their in Vitro Anticancer Activity.

Four new octanuclear Ru(II) cages (OC-1-OC-4) were synthesized from dinuclear p-cymene ruthenium(II) acceptors [Ru2(µ-η4-C2O4)(CH3OH)2(η6-p-cymene)2](O3SCF3)2 (A1), [Ru2(µ-η4-C6H2O4)(CH3OH)2(η6-p-cymene)2](O3SCF3)2 (A2), [Ru2(dhnq)(H2O)2(η6-p-cymene)2](O3SCF3)2 (A3), and [Ru2(dhtq)(H2O)2(η6-p-cymene)2](O3SCF3)2 (A4) separately with a tetradentate pyridyl ligand (L1) in methanol using coordination-driven self-assembly [L1= N,N,N',N'-tetra(pyridin-4-yl)benzene-1,4-diamine]. The octanuclear cages are fully characterized by various spectroscopic techniques including single-crystal X-ray diffraction analysis of OC-4. The self-assembled cages show strong in vitro anticancer activity against human lung adenocarcinoma A549 and human cervical cancer HeLa cell lines as observed from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Of all the octanuclear cages, OC-3 exhibits remarkable anticancer activity against both cancer cell lines and is more active than that reported for cisplatin. The excellent anticancer activity of OC-3 and OC-4 highlights the importance of the synergistic effects of the spacer component of the dinuclear p-cymene Ru(II) acceptor clips.

Water-Soluble Pd8L4 Self-assembled Molecular Barrel as an Aqueous Carrier for Hydrophobic Curcumin.

A tetrafacial water-soluble molecular barrel (1) was synthesized by coordination driven self-assembly of a symmetrical tetrapyridyl donor (L) with a cis-blocked 90° acceptor [cis-(en)Pd(NO3)2] (en = ethane-1,2-diamine). The open barrel structure of (1) was confirmed by single crystal X-ray diffraction. The presence of a hydrophobic cavity with large windows makes it an ideal candidate for encapsulation and carrying hydrophobic drug like curcumin in an aqueous medium. The barrel (1) encapsulates curcumin inside its molecular cavity and protects highly photosensitive curcumin from photodegradation. The photostability of encapsulated curcumin is due to the absorption of a high proportion of the incident photons by the aromatic walls of 1 with a high absorption cross-sectional area, which helps the walls to shield the guest even against sunlight/UV radiations. As compared to free curcumin in water, we noticed a significant increase in solubility as well as cellular uptake of curcumin upon encapsulation inside the water-soluble molecular barrel (1) in aqueous medium. Fluorescence imaging confirmed that curcumin was delivered into HeLa cancer cells by the aqueous barrel (1) with the retention of its potential anticancer activity. While free curcumin is inactive toward cancer cells in aqueous medium at room temperature due to negligible solubility, the determined IC50 value of ∼14 µM for curcumin in aqueous medium in the presence of the barrel (1) reflects the efficiency of the barrel as a potential curcumin carrier in aqueous medium without any other additives. Thus, two major challenges of increasing the bioavailability and stability of curcumin in aqueous medium even in the presence of UV light have been addressed by using a new supramolecular water-soluble barrel (1) as a drug carrier.

Synthesis, molecular docking and evaluation of antifungal activity of Ni(II), Co(II) and Cu(II) complexes of porphyrin core macromolecular ligand.

Porphyrin core dendrimeric ligand (L) was synthesized by Rothemund synthetic route in which p-hydroxy benzaldehyde and pyrrole were fused together. The prepared ligand was complexed with Ni(II), Cu(II) and Co(II) ions, separately. Both the ligand and its complexes were characterized by elemental analysis and spectroscopic studies (FT-IR, UV-Vis, (1)HNMR). Square planar geometries were proposed for Cu(II), Ni(II) and Co(II) ions in cobalt, Nickel and copper complexes, respectively on the basis of UV-Vis spectroscopic data. The ligand and its complex were screened on Candida albicans (ATCC 10231), Aspergillus fumigatus (ATCC 1022), Trichophyton mentagrophytes (ATCC 9533) and Pencillium marneffei by determining MICs and inhibition zones. The activity of the ligand and its complexes was found to be in the order: CuL ˃ CoL ≈ NiL ˃ L. Detection of DNA damage at the level of the individual eukaryotic cell was observed by commet assay. Molecular docking technique was used to understand the ligand-DNA interactions. From docking experiment, we conclude that copper complex interacts more strongly than rest two.

A Pd24 Pregnant Molecular Nanoball: Self-Templated Stellation by Precise Mapping of Coordination Sites.

We found that Pd(II) ion (M) and the smallest 120° bidentate donor pyrimidine (L(a)) self-assemble into a mononuclear M(L(a))4 complex (1a) instead of the expected smallest M12(L(a))24 molecular ball (1), presumably due to the weak coordination nature of the pyrimidine. To construct such a pyrimidine bridged nanoball, we employed a new donor tris(4-(pyrimidin-5-yl)phenyl)amine (L); which upon selective complexation with Pd(II) ions resulted in the formation of a pregnant M24L24 molecular nanoball (2) consisting of a pyrimidine-bridged Pd12 baby-ball supported by a Pd12 larger mother-ball. The formation of the baby-ball was not successful without the support of the mother-ball. Thus, we created an example of a self-assembly where the inner baby-ball resembling to the predicted M12(L(a))24 ball (1) was incarcerated by the giant outer mother-ball by means of geometrical constraints. Facile conversion of the pregnant ball 2 to a smaller M12(L(b))24 ball 3 with dipyridyl donor was achieved in a single step.

Clinical Spectrum of Acute Post-streptococcal Glomerulonephritis in Children: A Kashmir Experience.

Background In the pediatric population, acute post-streptococcal glomerulonephritis (PSGN) is a common glomerular etiology of hematuria and acute hypertension leading to hospitalization. We conducted this study to know the clinical profile and occurrence of acute PSGN in patients presenting with features of acute nephritic syndrome. Methods This prospective observational study was conducted on children aged between two and 18 years, presenting with clinical features of acute glomerular nephritis (AGN). After due ethical considerations, all eligible patients were enrolled and underwent detailed clinical assessment, laboratory, and imaging evaluation, followed by protocolized treatment. Relevant data were collected and analyzed to reach valid results. Results Out of 60 patients with AGN, PSGN was found in 83.3% of the patients (50/60). The age group under five years was the most commonly involved, with a male/female ratio of 1.6:1. Around half of the studied patients were from the lower middle class, and 40 (80%) were from rural backgrounds. Facial puffiness was the most common clinical presentation, seen in 45 (90%) patients. Hypocomplementemia and proteinuria were seen in all PSGN patients. Pyoderma was the most common preceding infection, seen in 38 (76%) patients, followed by pharyngitis. Acute kidney injury (AKI) was the most common complication, seen in 12 (24%) patients. Complete resolution of the signs and symptoms was seen in 37 (74%) patients at the time of discharge, which increased to 47 (94%) patients at six months post discharge. Conclusion PSGN stands to be the most common cause of pediatric AGN. The population under five years of age, with a past history of pyoderma, is more predisposed to PSGN. The potential for the occurrence of AKI and other life-threatening complications is high, for which early diagnosis and institution of proper treatment would be very beneficial.

Light-absorbing impurities in glacial environments over western Himalaya from reanalysis data and in situ observations.

In context with the scientific evidence of aerosol deposition induced snow and glacier melt, this paper provides baseline information about the spatiotemporal variability of aerosols and snow-ice chemistry filling the data and knowledge gap over the western Himalaya, India based on recently published paper [1]. A systematic approach was employed that entailed analysis of aerosol variability over four decades using MERRA-2 (Modern-Era Retrospective analysis for Research and Applications) data over five major mountain ranges in the western Himalaya. Further, data about nine physicochemical parameters was generated over three selected glaciers in the study area. HYSPLIT (HYbrid Single Particle Lagrangian Integrated Trajectory) model simulated air mass sources at weekly intervals. This dataset is valuable for future investigations aimed at understanding and characterizing the impacts of light-absorbing impurities on radiative forcing, albedo changes, snow-melt, glacier recession and water quality in the western Himalaya.

Metabolic Abnormalities, Inflammatory Markers and Endothelial Dysfunction in Hyperprolactinemia due to Prolactinoma before and after Normalization of Serum Prolactin: A Prospective Case Control Study.

Background: Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists. Methodology: Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks. Results: The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1. Conclusion: Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA.

Effect of in situ mixed micellization of ester-functionalized gemini surfactant at different pHs on solubilization and cosolubilization of various polycyclic aromatic hydrocarbons of varying hydrophobicities.

A pH controlled cleavability unfolds the 3-in-1 surfactant feature of an ester-bonded gemini surfactant, 2, 2'-[(oxybis (ethane-1,2-diyl))bis (oxy)]bis (N-hexadecyl-N,Ndimethyl-2-oxoethanaminium) dichloride (C16-C4O2-C16), by reinforcing in-situ mixed micellization between cleaved components at non-neutral pH (pH 3,12). The triplicity is assigned to two mixed-micelle variants at pH 3 and pH 12 besides the unhydrolyzed C16-C4O2-C16 at pH 7. The pH-controlled aggregation of such trichotomic surfactant dramatically enhances the micellar solubilization/cosolubilization of PAHs viz. naphthalene (Np), phenanthrene (Ph), pyrene (Py), perylene (Pe). The cosolubilization of binary/ternary PAH mixtures in such remarkable micellar assemblies at pH 3, 7 and 12 yields intriguing synergistic or antagonistic solubility outcomes correlated to PAH-PAH and PAH-micelle interactions. This study provides valuable insights into the potential applications of the ester-bonded gemini surfactant for the cosolubilization of undesirable hydrophobic compounds at natural sites having variable pH.

Neuromyelitis optica spectrum disorders.

The disease concept of Neuromyelitis Optica Spectrum Disorders(NMOSD) has undergone a significant change over the last two decades including the detection of Myelin Oligodendrocyte Glycoprotein(MOG) antibody in patients who are seronegative for aquaporin-4 antibody. Aquaporin-4 antibody positive NMOSD is now regarded as an immune astrocytopathy. Conversely, MOG antibody associated disease is known to target myelin rather than astrocytes, leading to an NMOSD syndrome with distinct clinical and radiological features. Incorporation of clinical features like area postrema syndrome, brainstem syndrome, diencephalic syndrome and cortical manifestations as core clinical characteristics into the revised diagnostic criteria has widened the clinical spectrum of NMOSD. With the development of these criteria, it is possible to make the diagnosis at an earlier stage so that effective immunosuppression can be instituted promptly for a better long-term prognosis. Newer therapeutic agents have been introduced for aquaporin-4 seropositive NMOSD disease; however, challenges remain in treating seronegative disease because of limited treatment options.

Molecular recognition and adsorptive separation of m-xylene by trianglimine crystals.

The separation of xylene isomers is one of the most challenging tasks in the petrochemical industry. Herein, we developed an efficient adsorptive molecular sieving strategy using crystalline trianglimine macrocycle (1) to separate the elusive m-xylene isomer from an equimolar xylenes mixture with over 91% purity. The selectivity is attributed to the capture of the preferred guest with size/shape selectivity and C-H⋯π interactions. Moreover, the trianglimine crystals are readily recyclable due to the reversible transformation between the guest-free and guest-loaded structures.

Conformational and solution dynamics of hemoglobin (Hb) in presence of a cleavable gemini surfactant: Insights from spectroscopy, atomic force microscopy, molecular docking and density functional theory.

Herein, we have explored the conformational alterations of hemoglobin (Hb) in presence of a cleavable gemini surfactant (C16-C4O2-C16). The concerned surfactant was found to induce significant structural perturbations in Hb. UV-vis spectroscopy, steady-state/time-resolved fluorescence, and other utilized techniques have authenticated the complexation of Hb with the gemini surfactant. CD has demonstrated the alterations in secondary structural elements (α-helicity, ß-sheet, ß-turn, and random coil) of Hb upon C16-C4O2-C16 addition. Atomic force microscopy (AFM) has revealed the existence of unique star-shaped gemini surfactant microstructures aligned to Hb in a necklace pattern. The 1H NMR peak broadening and lower delta values hint at the binding of the concerned gemini surfactant to Hb. Molecular docking and DFT calculations have further substantiated the Hb-gemini complex formation and the involvement of electrostatic/hydrophobic forces therein. In future, these results might pave-the-way to construct self-assembled, sustainable, and green surfactant-protein mixtures for their end-use in industrial, engineering, biomedical, drug delivery, gene transfection, and other relevant excipient formulations.

Solution behaviour of lysozyme in the presence of novel biodegradable gemini surfactants.

Extensive applications of biomacromolecule-surfactant mixtures in cosmetics, industry, agriculture, laundry and biomedical realms have raised environmental and ecological issues. Therefore, scientists now-a-days are concerned to design environmentally benevolent surfactant-protein mixtures which are not only efficient, but ecological too. In this context, we have studied the solution behaviour of hen egg white lysozyme (HEWL) in the presence of two novel biodegradable gemini surfactants by utilizing various spectroscopic and computational methods. The results confirmed the complex formation between Cm-E2O-Cm and HEWL via static mechanism and hydrophobic forces were found to be major contributing forces during interactions. C12-E2O-C12 was found to bind strongly to HEWL than C14-E2O-C14, owing to its smaller size and better penetration efficacy into the hydrophobic domains of HEWL. Upon Cm-E2O-Cm addition, conformational/microenvironmental alterations in HEWL were revealed, respectively, by circular dichroism and pyrene micro-polarity studies. Molecular modeling demonstrates that Cm-E2O-Cm binds in the locality of aromatic residues (Trp/Tyr). This study in future may lend a hand in designing safe and environmentally green surfactant-protein mixtures for their ultimate exploitation in food, laundry, and agriculture prefecture.

Interaction of a novel twin-tailed oxy-diester functionalized surfactant with lysozyme: Spectroscopic and computational perspective.

Herein, we have examined the interaction of oxy-diester novel twin tailed (gemini) surfactant, 2,2'-[(oxybis(ethane-1,2-diyl))bis(oxy)]bis(N-hexadecyl-N,Ndimethyl-2-oxoethanaminium) dichloride (C16-E2O-C16) with hen egg white lysozyme (HEWL), utilizing a spectroscopic and molecular docking techniques. Steady-state fluorescence infers ground state C16-E2O-C16-HEWL complex formation. Other spectroscopic results validated the conformational, structural and micro-environmental changes in HEWL upon interaction with C16-E2O-C16. Molecular modeling has shown that C16-E2O-C16 binds in the proximity of hydrophobic moieties (Trp-62/108). We believe the results of the current study will assist in designing the surfactant-enzyme systems for their end use as ingredients in pharmaceutical, cosmetic, drug delivery and industrial compilations. In terms of scientific literature standpoint, it will also enrich and widen the scope of biomacromolecule-surfactant interactions.

Coordination-driven self-assembly of ruthenium(ii) architectures: synthesis, characterization and cytotoxicity studies.

Coordination-driven self-assembly of organometallic η6-arene ruthenium(ii) supramolecular architectures (MA1-MA4) was carried out by employing dinuclear ruthenium acceptors [Ru2(µ-η4-C2O4)(CH3OH)2(η6-p-cymene)2](CF3SO3)2 (Rua), [Ru2(µ-η4-C6H2O4)(CH3OH)2(η6-p-cymene)2](CF3SO3)2 (Rub), [Ru2(dhnq)(H2O)2(η6-p-cymene)2](CF3SO3)2 (Ruc) and [Ru2(dhtq)(H2O)2(η6-p-cymene)2](CF3SO3)2 (Rud) separately with a new tetratopic donor (TD) in methanol at room temperature [TD = N,N,N',N'-tetra(pyridin-4-yl)-[1,1'-biphenyl]-4,4'-diamine]. All the coordination architectures were characterized by using spectroscopic techniques. The potency of these self-assembled architectures against human cervical cancer HeLa and human lung adenocarcinoma A549 cell lines is explored in vitro using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), annexin V-FITC/PI and 2',7'-dichlorofluorescein-diacetate assays.

Preparation of a chiral Pt12 tetrahedral cage and its use in catalytic Michael addition reaction.

The reaction of chiral cis-[(1S,2S)-dch]Pt(NO3)2 (M) [where (1S,2S)-dch = (1S,2S)-1,2-diaminocyclohexane] with a hexadentate ligand (L) in 3 : 1 stoichiometric ratio yielded a [12+4] self-assembled chiral M12L4 molecular tetrahedron (T). The cage T features an internal 3D nanocavity with large open 'windows', enabling it to catalyze Michael addition reactions of a series of nitrostyrene derivatives with indole in a 9 : 1 water : methanol mixture.

Role of the Functional Polymorphism of Survivin Gene (-31G/C) and Risk of Breast Cancer in a North Indian Population.

INTRODUCTION: Survivin is an apoptosis inhibitor and plays a primary role in cancer development and progression. One of the most common polymorphism of the survivin promoter -31G/C (rs9904341) influences its expression and is associated with the risk of cancer development. This study was conducted to explore survivin promoter gene -31G/C (rs9904341) polymorphism and the risk of breast cancer. PATIENTS AND METHODS: The study group included 190 pathologically confirmed breast cancer patients, in addition to 200 distinct cancer-free controls from Jammu and Kashmir region of India, where breast cancer is the most common cancer in women. Single nucleotide polymorphism genotyping for -31G/C polymorphism in the survivin promoter region was done using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The variant genotype/allele was found in 54.1% of the cases compared with 46.5% of controls. The combined prevalence of genotype GC+CC was significantly higher in patients compared with the control group (P = .02). Analyses of odds ratios (ORs) in the patient and control groups indicated that the presence of homozygous CC genotype was associated with increased risk for development of breast cancer (OR, 2.04; 95% confidence interval [CI], 1.07-2.98). The gene frequencies for G and C alleles were statistically different between patient and control groups (OR, 1.37; 95% CI, 1.03-1.84). CONCLUSION: The results suggest the association of -31G/C survivin polymorphism at a genotypic and allelic level in breast cancer.