Comparative Study in Locally Advanced Breast Cancer Treated with Either Cyclophosphamide, Adriamycin, 5-Flourouracil Regimen or Adriamycin, Cyclophosphamide Followed by Paclitaxel

Introduction:Carcinoma breast is the leading cause of death among the cancer patients worldwide. Carcinoma breast is not a single entity but spectrum of diseases. Aims and objectives:This is a prospective two arm comparative study of toxicity and quality of life in patients of locally advanced breast cancer treated with either cyclophosphamide, Adriamycin, 5-flourouracil regimen or Adriamycin, cyclophosphamide followed by paclitaxel.Materials and methods:The study is a prospective randomized two arm study conducted in department of radiotherapy, For a period of 2 years on breast cancer patients treated divided as Patients in CAF (ARM-A) received cyclophosphamide 600mg/m2, Adriamycin 60mg/m2, 5-flourouracil 600mg/m2 as intravenous infusion on day 1 and repeated every 3 weekly for 6 cycles. Patients in ARM-B received cyclophosphamide 600mg/m2, Adriamycin 60mg/m2, as IV infusion every 3 weekly for 4 cycles followed by paclitaxel 175mg/m2 every 3 weekly for 4 cycles. Pre-medication include Ondansetron 8mg , dexamethasone 8mg intravenous push and pantoprazole 40 mg as intravenous infusion.Results:The maximum incidence was observed between 41-50yrs of age in both arms.The most common presentation was postmenopausal status 46.6% in CAF arm and 36.6% in TAC arm. Most common stage of presentation was stage IIIA , 55% in CAF and 48.3% in TAC arm. 75% patients in CAF arm and 63% patients in TAC arm were ER positive.Complete clinical response after neoadjuvant chemotherapy was seen more in TAC arm (16.6%). Among all toxicities alopecia was significant statistically. Peripheral neuropathy was higher in TAC arm. Diarrhea was higher in CAF arm. Nausea and vomiting were similar in both arms. Better quality of life was seen in TAC arm patients.Conclusion: Neoadjuvant chemotherapy integrated into a multimodality program is the established treatment in LABC. Paclitaxel based regimen showed significant increase in complete clinical response of tumor

Strontium eluting nanofibers augment stem cell osteogenesis for bone tissue regeneration

Strontium is known to offer a therapeutic benefit to osteoporotic patients by promoting bone formation. Thus, toward engineering scaffolds for bone tissue regeneration we have prepared polymer nanocomposite scaffolds by electrospinning. Strontium carbonate nanoparticles (nSrCO(3)) were added to poly(epsilon-caprolactone) (PCL) at 10 and 20 wt% to develop nanocomposite fibrous scaffolds (PCL/SrC10 and PCL/SrC20) with fiber diameter in the range of 300-500 nm. Incorporation of nSrCO(3) decreased crystallinity and the elastic modulus of PCL. The composite scaffolds released Sr2+ ions with up to 65 ppm in 4 days from the PCL/SrC20 scaffolds. Cell studies confirmed that the composite scaffold with 20% nSrCO(3) enhanced proliferation of human mesenchymal stem cells in vitro. There was marked increase in mineral deposition up to four folds in PCL/SrC20 suggesting enhanced osteogenesis. This was corroborated by increased mRNA and protein expression of various osteogenic markers such as BMP-2, Osterix and Runx2 in the PCL/SrC20 fibers. Thus, incorporation of nSrCO(3) in polymer scaffolds is a promising strategy for bone tissue engineering as an alternative to the use of labile growth factors to impart bioactivity to polymer scaffolds. (C) 2016 Elsevier B.V. All rights reserved

Curcumin eluting nanofibers augment osteogenesis toward phytochemical based bone tissue engineering

Curcumin is a phenolic compound isolated from Curcuma longa that is known to exhibit wide ranging biological activity including potential benefits for bone growth. The aim of this work was to engineer curcumin eluting tissue scaffolds and investigate their potential use in bone tissue regeneration. We prepared curcumin loaded poly(e-caprolactone) (PCL) nanofibers by electrospinning. Morphological characterization of the nanofibers revealed that the average diameter of neat fibers and that of fibers with 1 wt% and 5 wt% curcumin is 840 +/- 130 nm, 827 +/- 129 nm and 680 +/- 110 nm, respectively. Fourier transformation infrared spectroscopy and H-1 nuclear magnetic resonance confirmed the successful loading of the drug in fibers. In aqueous medium, the fibers released approximate to 18% of the encapsulated drug in 3 d and approximate to 60% in 9 d. The cell response to the curcumin loaded nanofibers was assessed using MC3T3-E1 pre-osteoblasts. Cell proliferation was moderated with increased loading of curcumin and was 50% lower on the fibers containing 5% curcumin at day 10 than the control fibers. Osteogenesis was confirmed by assaying the expression of alkaline phosphatase and staining of mineral deposits by Alizarin red stain, which were both markedly higher for 1% curcumin compared to neat polymer but lower for 5% curcumin. Mineral deposition was also confirmed chemically by Fourier transform infrared spectroscopy. These results were corroborated by increased gene and protein expression of known osteogenic markers in 1% curcumin. Thus, controlled release of curcumin from polymer scaffolds is a promising strategy for bone tissue regeneration

In situ preparation of multicomponent polymer composite nanofibrous scaffolds with enhanced osteogenic and angiogenic activities

Bioactive ceramics are extensively used for bone repair and regeneration, which release ions to initiate apatite formation and promote osteogenic differentiation eventually resulting in strong bonding to bone. Toward enhancing the bioactivity of polymeric nanofibrous scaffolds, this work presents a one-step in situ sol-gel method to fabricate electrospun composite nanofibrous scaffolds encapsulating well dispersed ceramic nanoparticles overcoming the limitations of current preparation techniques. Transmission electron micrographs revealed uniform distribution of ceramic nanoparticles within the polymer nanofibers. The multicomponent scaffolds were found to release calcium, silicon and phosphate ions that mimic the dissolution and bioactivity of conventional bioactive glasses. The scaffolds enhanced the bioactivity of PCL fibers as observed through enhanced apatite formation in simulated body fluid. The released ions markedly enhanced the proliferation and osteogenic differentiation of human mesenchymal stem cells and the angiogenic activity of human endothelial cells in vitro. This work has important implications for engineering the next-generation nanostructured scaffolds that exhibit multi-biofunctional activities for bone tissue regeneration

Synthesis of a Block Copolymer Exhibiting Cell-Responsive Phytochemical Release for Cancer Therapy

Phytochemicals constitute a promising class of therapeutics for the treatment of various diseases, but, their delivery poses significant challenges. In this work, a nanoscale polyactive emulsion was designed for smart, cell-responsive delivery of a curcumin prodrug (curcumin dicarboxylate, CDA) that was chemically conjugated to enzymatically labile oligo-peptides with polycaprolactone (PCL) as the carrier. Matrix metalloproteinase (MMP)-sensitive (PLGLYAL) or nonsensitive (GPYYPLG) peptides were used as spacers for conjugating CDA and PCL. This CDA nanoemulsion incorporating the MMP-sensitive sequence exhibited markedly higher anti-cancer activity, cell internalization, and generation of reactive oxygen species in cancer cells in vitro than the control with the nonsensitive oligopeptide. Moreover, the nanopolyactives induced minimal cytotoxicity in noncancerous cell line. This work presents a unique strategy to engineer smart nano-polyactives for efficient and targeted delivery of phytochemicals

A self-assembling polycationic nanocarrier that exhibits exceptional gene transfection efficiency

The lack of an efficient and safe carrier is a major impediment in the field of gene therapy. Although gelatin (GT), a naturally derived polymer, is widely used in drug delivery applications, it is unable to bind DNA efficiently. In this study, a novel polycationic gene carrier was prepared by conjugation of low molecular weight polyethyleneimine (LPEI) with GT through 4-bromonaphthaleic anhydride as a coupling agent to avoid self crosslinking. Self-assembly of LPEI conjugated GT (GT-LPEI) with plasmid DNA (pDNA) yielded nanoparticles with high gene complexation ability to form similar to 250 nm cylindrical nanoparticles with a zeta potential of similar to 27 mV. GT-LPEI showed exceptionally high transfection efficiency (> 90%) in various mammalian cells including primary stem cells with minimal cytotoxicity. The transfection efficiency of GT-LPEI significantly surpassed that of many commercial reagents. The high gene transfection expression was confirmed in vivo. Thus, GT-LPEI is shown to be a promising nonviral carrier for potential use in gene therapy

In Situ Silication of Polymer Nanofibers to Engineer Multi-Biofunctional Composites

The critical role of silica in bone homeostasis has motivated the development of silica-based biomaterials for orthopedic applications. Whereas polymer nanofibers have emerged as promising substrates for orthopedic applications, nanoparticle agglomeration precludes the preparation of silica containing composite nanofibers by electrospinning. This work presents a facile sol-gel process to fabricate electrospun nanocomposite fibers by insitu silica gelation in poly (epsilon-caprolactone) (PCL) solution. Citric acid is shown to be more effective than acetic acid as the pH catalyst for gelation by rapidly yielding near uniform nanoparticles (150 +/- 50 nm). The composite nanofibers exhibited increased water wettability than neat PCL with sustained release of silicon ions. The composite fibers induced early apatite formation in simulated body fluid. Quantitative characterization of the tubular networks formed by human umbilical cord vascular endothelial cells revealed that the eluted silicon ions and citric acid in fibers synergistically promoted angiogenic activity, which was corroborated by increased gene and protein expressions of several known angiogenic markers. Furthermore, silicate fibers augmented osteogenesis of human mesenchymal stem cells as measured by the increased mineral deposition and increased gene and protein expression of osteogenic markers. Thus, the insitu silicated fibers are promising multi-biofunctional materials for orthopedic applications

Engineering a Piperine Eluting Nanofibrous Patch for Cancer Treatment

The objective of this study was to engineer a biodegradable polymeric system for sustained release of piperine for cancer treatment. We prepared nanofibrous patches of poly­(ε-caprolactone) (PCL) and gelatin (GEL) blends of different ratios by electrospinning. The PCL/GEL nanofibers were loaded with up to 30 wt % piperine, a phytochemical derived from black pepper, which is believed to exhibit anticancer, antiarthritis, antibacterial, antioxidant, and anti-inflammatory properties. Scanning electron microscopy revealed that the fiber diameter was in the range of 300–400 nm. Fourier-transform infrared spectroscopy confirmed that the drug was successfully loaded into the nanofiber mats. In vitro release kinetics revealed the sustained release of the drug with 50% release in 3 days from the PCL/GEL (50:50 by weight) blend fibers. The reduced viability and growth of HeLa and MCF-7 cancer cells on the piperine eluting nanofibers demonstrated anticancer activity in vitro. The proliferation of noncancerous cells such as NIH3T3 cells and human mesenchymal stem cells was affected to a markedly lesser extent. Flow cytometry revealed that the released piperine induced the generation of reactive oxygen species (ROS) and cell cycle arrest in the G2/M phase, leading to cell death of cancer cells. The findings of this study suggest that piperine-loaded nanofiber mats could be developed into implantable biodegradable patches for use in postsurgical cancer treatment

Gender prediction by using radio morphometric analysis of frontal sinus parameters – A prospective study with cone beam computed tomography

Introduction: Radiology is an essential branch of medicine well known for its nature as “seeing the unseen.” It is now extending its wings to the field of forensics to “identify the unseen” during mass disasters and natural calamities. Even after catastrophes, parts of the facial skeleton, such as the maxillary sinus, frontal sinus, and other alternate sections of the human facial skeleton, are being explored for sex identification. Researchers have proven that the frontal sinus is also a valuable tool for assessing the gender of a person. The frontal sinus and its structural diversity suggest that it is an important anatomical area to be analyzed for forensic purposes, notably in identifying sex using skull dimensions. Hence, this study aimed to identify sexual dimorphism by evaluating the frontal sinus using cone beam computed tomography (CBCT). Materials and Methods: In this study, a total of 50 patients were selected and were divided into two groups, group I (25 males) and group II (25 females), where the frontal sinus height (superioinferior) and width (mediolateral) dimensions were evaluated using CBCT scans All the measurements were performed in coronal sections. Results: The independent t-test and Mann–Whitney U-test were used to analyze the data. Shapiro–Wilk test was used to assess normality. Right frontal sinus height (P-0.11) and width (P-0.1), and frontal sinus index (P-0.81) were higher in males than in females. Left frontal sinus height (P < 0.001), width (P < 0.001), and frontal sinus index (P-0.64) were higher in males than in females. Left frontal sinus height and width were statistically significant, depicting the sexual dimorphism. Conclusion: The gender predictor variable of the frontal sinus in the current study using parameters such as height, width, and frontal sinus index on CBCT was higher in males compared to females. Left frontal sinus can be considered as a useful predictor in the gender determination of the individual

Comparative evaluation of bovine derived hydroxyapatite and synthetic hydroxyapatite graft in bone regeneration of human maxillary cystic defects: A clinico-radiological study

Introduction: Bone grafts are frequently used in the treatment of bone defects. Bone harvesting can cause postoperative complications and sometimes does not provide a sufficient quantity of bone. Therefore, synthetic biomaterials have been investigated as an alternative to autogenous bone grafts. Aim and Objectives: The aim of this study was to evaluate and compare bovine derived hydroxyapatite (BHA) and synthetic hydroxyapatite (SHA) graft material as bone graft substitute in maxillary cystic bony defects. Patients were analyzed by computerized densitometric study and digital radiography. Materials and Methods: In this study, 12 patients in each group were included randomly after clinical and radiological evaluation. The integration of hydroxyapatite was assessed with mean bone density, surgical site margin, and radiological bone formation characteristics, of the successful graft cases using computer densitometry and radio-visiograph. Statistical analysis was carried out using Mann-Whitney U-test, Wilcoxon matched pairs test and paired t-test. Results: By the end of 24 th week, the grafted defects radiologically and statistically showed similar volumes of bone formation. However, the significant changes observed in the formation of bone and merging of material and surgical site margin at 1 st week to 1 st month. The results were significant and correlating with all the parameters showing the necessity of the grafting for early bone formation. However, the bone formation pattern is different in both BHA and SHA group at 3 rd month interval with significant P value. Conclusion: Both BHA and SHA graft materials are biocompatible for filling bone defects, showing less resorption and enhanced bone formation with similar efficacy. Our study showed maximum bone healing within 12 weeks of grafting of defects. The BHA is economical; however, price difference between the two is very nominal