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1.
Molecules ; 27(23)2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36500331

ABSTRACT

The emerging concepts of sustainable textiles and controlled production strategy demands ideally zero emissions of contaminants into the aquatic environment. However, the currently in-practiced conventional processes in textiles dispose of a number of contaminants especially super toxic synthetic dyes as effluents. In recent years, nanomaterials have become attractive choice for eco-friendly removal of organic dyestuff. Accordingly, this article reports synthesis and characterization of biocomposite wherein copolymer of polyaniline (PANI) and Polypyrrole (PPY) was grafted onto hydroxyethyl cellulose (HEC). Further, adsorption properties of as-prepared composite were evaluated using textile dyes Rhodamine B (RhB) and methyl Orange (MO)- as model adsorbate. The characterization of novel biocomposite (HEC/PANI-PPy) was carried out using Fourier Transform Infrared (FT-IR), Brunauer-Emmett-Teller analyzer (BET), Scanning Electron Microscope (SEM), and powder X-ray diffraction (XRD). The operational parameters such as dye initial concentration, adsorbent amount, pH and contact time were also studied to evaluate the efficiency level of the prepared biocomposite. Interestingly, the composite-mediated adsorption of RhB and MO followed pseudo-second order and the Langmuir isotherm. It is found that the adsorption capacity HEC/PANI-PPy is 30.06 and 29.3 for RhB and MO respectively. Thus, HEC/PANI-PPy is an inexpensive and highly efficient adsorbent that could be employed for could be employed for the separation and removal of toxic organic dyes from polluted textile effluents.


Subject(s)
Coloring Agents , Water Pollutants, Chemical , Coloring Agents/chemistry , Polymers/chemistry , Pyrroles/chemistry , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/chemistry , Adsorption , Cellulose , Kinetics
2.
Molecules ; 27(22)2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36431778

ABSTRACT

In the present work, sulfur-doped manganese ferrites S@Mn(Fe2O4) nanoparticles were prepared by using the sol-gel and citrate method. The concentration of sulfur varied from 1 to 7% by adding Na2S. The samples were characterized by performing Fourier Transformed Infrared Spectroscopy (FTIR), Energy Dispersive X-ray (EDX), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Ultraviolet-Visible spectroscopy (UV-Visible). The synthesized sulfur-doped manganese ferrites were applied to evaluate the photocatalytic degradation of the dyes. Further, the degradation studies revealed that the nanoparticles successfully degraded the methylene blue dye by adding a 0.006 g dose under the sunlight. The sulfur-doped manganese ferrite nanoparticles containing 3% sulfur completely degraded the dye in 2 h and 15 min in aqueous medium. Thus, the ferrite nanoparticles were found to be promising photocatalyst materials and could be employed for the degradation of other dyes in the future.


Subject(s)
Nanoparticles , Sunlight , Manganese/chemistry , Catalysis , Nanoparticles/chemistry , Coloring Agents/chemistry , Cations , Sulfur
3.
Molecules ; 27(17)2022 Aug 26.
Article in English | MEDLINE | ID: mdl-36080245

ABSTRACT

The synthesis of MMT and poly(o-anisidine) (MMT/POA) clay nanocomposites was carried out by using the chemical oxidative polymerization of POA and MMT clay with POA, respectively. By maintaining the constant concentration of POA, different percentage loads of MMT clay were used to determine the effect of MMT clay on the properties of POA. The interaction between POA and MMT clay was investigated by FTIR spectroscopy, and, to reveal the complete compactness and homogeneous distribution of MMT clay in POA, were assessed by using scanning-electron-microscope (SEM) analysis. The UV-visible spectrum was studied for the optical and absorbance properties of MMT/POA ceramic nanocomposites. Furthermore, the horizontal burning test (HBT) demonstrated that clay nanofillers inhibit POA combustion.


Subject(s)
Flame Retardants , Nanocomposites , Aniline Compounds , Bentonite/chemistry , Clay , Nanocomposites/chemistry
4.
Environ Sci Pollut Res Int ; 28(36): 49958-49966, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33948834

ABSTRACT

Environmental friendly products particularly natural dyes are going to be much popular around the globe due to their non-toxic and bio-degradable nature. The current study was planned to enhance the dyeability of walnut bark having juglone as a reddish-brown natural dye under ultrasonic radiation as an environment-friendly and green tool After conducting series of experiments, it has been found that wool (RW) and extract (RE) after ultrasonic treatment for 45 min, when dyed for 45 min at 55°C using an acidic bath of 3 pH has given good color strength on the wool fabric. To develop the new shades, sustainable and eco-label chemicals (Fe, Al, and tannic acid) and four bio-mordants such as Acacia bark, Turmeric, Henna, and Pomegranate were also applied at optimum conditions. It is studied that 3% of turmeric extract as pre-bio-mordant and 5% of Acacia extract as post-bio-mordant has given excellent color characteristics as compared to their synthetic. It is concluded that ultrasonic treatment being an eco-friendly tool has a great potential to improve the dyeability of natural reddish-brown dye from walnut bark and the inclusion of sustainable biosources as a color modifier has value-added the natural dyeing process with excellent color ratings.


Subject(s)
Coloring Agents , Juglans , Animals , Naphthoquinones , Plant Bark , Wool , Wool Fiber
5.
J Food Prot ; 83(8): 1284-1288, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32678886

ABSTRACT

ABSTRACT: A total of 133 samples of whole wheat and barley grains and wheat and barley flour collected from retail markets in the main cities of Punjab, Pakistan, were analyzed for the mycotoxin fumonisin B1 (FB1) using reverse phase high-performance liquid chromatography with fluorescence detection. Of these samples, 120 (90%) were positive for FB1, and 75 (63%) of the 120 positive samples had FB1 concentrations higher than the European Union maximum (200 µg/kg). The limit of detection was 4 µg/kg. The highest mean (±SD) concentration of FB1 was found in whole wheat samples, 980.5 ± 211.4 µg/kg. The calculated dietary intakes of FB1 from wheat and barley flours were 4,456 and 503.7 ng/g of body weight per day, respectively.


Subject(s)
Fumonisins , Hordeum , Food Contamination/analysis , Fumonisins/analysis , Pakistan , Triticum
6.
Curr Org Synth ; 17(6): 457-463, 2020.
Article in English | MEDLINE | ID: mdl-32392115

ABSTRACT

BACKGROUND: The pyrano[2,3-c]pyrazole derivatives are important building blocks of many biologically active compounds owing to their diverse biological potential for example, anti-inflammatory, anticancer, anti-microbial and anti-oxidant properties. OBJECTIVE: Keeping in mind the wide range of applications of pyrano[2,3-c]pyrazoles, herein we intended to develop a novel synthetic methodology for dihydropyranopyrazoles. We were also interested in determining the influence of amino acids and dipeptides as a catalyst on the synthesis of pyrano[2,3-c]pyrazole derivatives. METHODS: To achieve our objectives, we used a one-pot multi-component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and several substituted benzaldehydes by using different catalysts and solvents to synthesize our desired products in the presence of various catalysts. RESULTS AND DISCUSSION: We found that optimal conditions for the preparation of pyrano[2,3-c]pyrazoles were L-cysteine (0.5 mol) in the presence of water:ethanol (9:1) at 90 °C. Various 1,4-dihydropyrano[2,3- c]pyrazoles were afforded by using several substituted benzaldehydes in 66-97% yields. CONCLUSION: We described a green and environmentally benign method to synthesize pyrano[2,3-c]pyrazoles in a one-pot four component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and different substituted benzaldehyde in the presence of L-cysteine in aqueous ethanol (9:1) at 90 oC. Excellent yields of the products, simple work-up, easily available starting materials, use of green solvents, naturally occurring catalyst, non-toxicity, non-chromatographic purification and environmentally benign reaction conditions are some main advantages of this protocol.


Subject(s)
Cysteine/chemistry , Pyrans/chemical synthesis , Pyrazoles/chemical synthesis , Benzaldehydes/chemistry , Catalysis , Green Chemistry Technology/methods , Water/chemistry
7.
Pak J Pharm Sci ; 32(6(Supplementary)): 2829-2834, 2019 Nov.
Article in English | MEDLINE | ID: mdl-32024621

ABSTRACT

Diabetes Mellitus is a chronic disease in which the infected cells do not have the ability to produce sufficient amount of insulin that resulted in the abnormality of carbohydrates metabolism and an increase in blood glucose level. Long time exposure to Diabetes Mellitus resulted in failure or dysfunction of different organs like kidneys, nerves, heart, eyes, etc. A common practice to cure diabetes is the use of α-glucosidase inhibitors which help in lowering the blood glucose level. We presented 1,2-benzothiazine 1,1-dioxide derivatives as novel and more potent α-glucosidase inhibitors via their in vitro and in silico screenings. Excellent enzyme inhibitions were observed for compounds 2, 8, 10 and 12 having IC50 values of 6.91, 14.0, 4.2, 5.9 and 29.2µ respectively which were found better than the reference acarbose (IC50=38.31µM). Molecular docking studies suggested high binding energies and good binding interactions of these compounds with the active site residues of the receptor protein. A good agreement was found between the results of both modes of evaluation. Moreover, the envisioned candidates have a good potential to treat diabetes.


Subject(s)
Diabetes Mellitus/drug therapy , Glycoside Hydrolase Inhibitors/pharmacology , Hydrazines/pharmacology , Hypoglycemic Agents/pharmacology , Thiazines/pharmacology , alpha-Glucosidases/metabolism , Acarbose/pharmacology , Humans , Kinetics , Molecular Docking Simulation/methods , Structure-Activity Relationship
8.
Chem Cent J ; 12(1): 46, 2018 Apr 26.
Article in English | MEDLINE | ID: mdl-29700704

ABSTRACT

Electrically conductive polyorthochloroaniline/chromium nanocomposites (POC/Cr NCs) were prepared by in situ chemical oxidative polymerization of orthochloroaniline in the presence of Cr nanoparticles (Cr NPs). The load percentage of Cr nanofiller was varied in POC matrix to investigate the effect of Cr nanoparticles on the properties of the nanocomposites. The composition, structure, and morphology of POC and its composites were examined by Scanning electron microscopy, Fourier transform infrared spectroscopy, and UV-visible spectroscopic analysis. The antibacterial potential of POC and its composites was evaluated by the disc diffusion method against Escherichia coli and Bacillus subtilis. The results showed the improved antibacterial potential with the increase in the load percentage of nanofiller. The electrical conductivity of polymer and its composites was measured and correlated with the load percentage. The results showed that electrical conductivity of the composites was enhanced with the increase in load percentage of Cr nanoparticles.

9.
J Food Prot ; 81(5): 806-809, 2018 05.
Article in English | MEDLINE | ID: mdl-29637809

ABSTRACT

Two hundred ten samples of selected vegetables (okra, pumpkin, tomato, potato, eggplant, spinach, and cabbage) from Faisalabad, Pakistan, were analyzed for the analysis of heavy metals: cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg). Inductively coupled plasma optical emission spectrometry was used for the analysis of heavy metals. The mean levels of Cd, Pb, As, and Hg were 0.24, 2.23, 0.58, and 7.98 mg/kg, respectively. The samples with Cd (27%), Pb (50%), and Hg (63%) exceeded the maximum residual levels set by the European Commission. The mean levels of heavy metals found in the current study are high and may pose significant health concerns for consumers. Furthermore, considerable attention should be paid to implement comprehensive monitoring and regulations.


Subject(s)
Food Contamination/analysis , Metals, Heavy/analysis , Vegetables/chemistry , Pakistan
10.
Int J Biol Macromol ; 79: 377-87, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25964178

ABSTRACT

The trend of using biopolymers in combination with synthetic polymers was increasing rapidly from last two or three decades. Polysaccharide based biopolymers especially starch, cellulose, chitin, chitosan, alginate, etc. found extensive applications for different industrial uses, as they are biocompatible, biodegradable, bio-renewable resources and chiefly environment friendly. Segment block copolymer character of polyurethanes that endows them a broad range of versatility in terms of tailoring their properties was employed in conjunction with various natural polymers resulted in modified biomaterials. Alginate is biodegradable, biocompatible, bioactive, less toxic and low cost anionic polysaccharide, as a part of structural component of bacteria and brown algae (sea weed) is quite abundant in nature. It is used in combination with polyurethanes to form elastomers, nano-composites, hydrogels, etc. that especially revolutionized the food and biomedical industries. The review summarized the development in alginate based polyurethanes with their potential applications.


Subject(s)
Alginates/chemistry , Biocompatible Materials/chemistry , Nanocomposites/chemistry , Polyurethanes/chemistry , Biodegradation, Environmental , Biomimetic Materials/chemistry , Cellulose/chemistry , Chitin/chemistry , Chitosan/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Humans , Hydrogels/chemistry , Polyurethanes/chemical synthesis
11.
Int J Biol Macromol ; 62: 670-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24120963

ABSTRACT

Hydroxy terminated polybutadiene (HTPB)-chitin based polyurethanes (PUs) with controlled hydrophobicity were synthesized using HTPB and toluene diisocyanate (TDI). The prepolymer was extended with different mass ratios of chitin and 1,4-butane diol (BDO). The effect of chitin contents in chain extender (CE) proportions on surface properties was studied and investigated. Incorporation of chitin contents into the final PU showed decrease in contact angle value of water drop, water absorption (%) and swelling behavior. The antibacterial activity of the prepared samples was affected by varying the chitin contents in the chemical composition of the final PU. The results demonstrated that the use of prepared material can be suggested as non-absorbable suture.


Subject(s)
Butadienes/chemistry , Chitin/chemistry , Elastomers/chemistry , Polyurethanes/chemistry , Absorption , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Hydrophobic and Hydrophilic Interactions , Molecular Structure , Polyurethanes/pharmacology , Surface Properties , Water/chemistry
12.
Ann Surg Oncol ; 20(5): 1514-21, 2013 May.
Article in English | MEDLINE | ID: mdl-23224829

ABSTRACT

BACKGROUND: Our purpose was to examine the incidence and impact on survival of other primary malignancies (OPM) outside of the breast in breast cancer patients and to identify risk factors associated with OPM. METHODS: Patients with stage 0-III breast cancer treated with breast conserving therapy at our center from 1979 to 2007 were included. Risk factors were compared between patients with/without OPM. Logistic regression was used to identify factors that were associated with OPM. Standardized incidence ratios (SIRs) were calculated. RESULTS: Among 4,198 patients in this study, 276 (6.6 %) developed an OPM after breast cancer treatment. Patients with OPM were older and had a higher proportion of stage 0/I disease and contralateral breast cancer compared with those without OPM. In a multivariate analysis, older patients, those with contralateral breast cancer, and those who did not receive chemotherapy or hormone therapy were more likely to develop OPM after breast cancer. Patients without OPM had better overall survival. The SIR for all OPM sites combined after a first primary breast cancer was 2.91 (95 % confidence interval: 2.57-3.24). Significantly elevated risks were seen for numerous cancer sites, with SIRs ranging from 1.84 for lung cancer to 5.69 for ovarian cancer. CONCLUSIONS: Our study shows that breast cancer patients have an increased risk of developing OPM over the general population. The use of systemic therapy was not associated with increased risk of OPM. In addition to screening for a contralateral breast cancer and recurrences, breast cancer survivors should undergo screening for other malignancies.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Gastrointestinal Neoplasms/epidemiology , Genital Neoplasms, Female/epidemiology , Lung Neoplasms/epidemiology , Neoplasms, Second Primary/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Chemotherapy, Adjuvant , Female , Humans , Incidence , Mastectomy, Segmental , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Risk Factors , Young Adult
13.
Cancer ; 110(12): 2640-7, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-17960791

ABSTRACT

BACKGROUND: Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases. METHODS: The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center. RESULTS: The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25-77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu-positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from -5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7-95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis. CONCLUSIONS: The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age.


Subject(s)
Breast Neoplasms/pathology , Central Nervous System Neoplasms/secondary , Adult , Aged , Disease-Free Survival , Female , Humans , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Time Factors
14.
Am J Surg ; 194(4): 527-31, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17826073

ABSTRACT

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.


Subject(s)
Adenocarcinoma, Mucinous/surgery , Adenocarcinoma/surgery , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Mastectomy, Segmental , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Time Factors , Treatment Outcome
15.
Dement Geriatr Cogn Disord ; 22(1): 48-53, 2006.
Article in English | MEDLINE | ID: mdl-16682793

ABSTRACT

BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42 )and tau differ between patients with Alzheimer's Disease (AD) and elderly normal controls. The effect of time and APOE genotype on these biomarkers continues to be elucidated. METHODS: We assessed CSF beta-amyloid(1-42) and tau in 20 mild-to-moderate AD patients, 11 APOE epsilon4+ and 9 APOE epsilon4-, over a mean time of 3.8 years (range 1-11.1 years). RESULTS: Over the period measured, CSF beta-amyloid(1-42) levels were lower in APOE epsilon4+ compared to APOE epsilon4- patients, and the levels decreased over time. Tau levels were stable over time and did not show an effect of APOE allele. CONCLUSIONS: While this is a limited clinical sample, the further decrease in CSF beta-amyloid(1-42 )(i.e., more abnormal) combined with the CSF tau stability over a mean period of almost 4 years suggests that beta-amyloid(1-42 )and tau maintain their potential usefulness as diagnostic biomarkers over time. These findings should be taken into account if CSF beta-amyloid(1-42) and tau are used as measures of treatment response.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/genetics , Amyloid beta-Peptides/cerebrospinal fluid , Apolipoproteins E/genetics , Peptide Fragments/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Aged , Alleles , Biomarkers , Female , Genotype , Humans , Male , Middle Aged , Neuropsychological Tests
16.
Neurobiol Aging ; 27(10): 1385-94, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16168525

ABSTRACT

Patients with minimal cognitive impairment (MCI) or Alzheimer's disease (AD) have smaller hippocampal volumes (HV) and increased rates of HV loss (rHVL). A 6-year study was conducted to assess rHVL in healthy aging subjects (HC) in which four MRI scans, each 2 years apart, were obtained on 26 HC with a mean age of 58.8 years when entering the study. rHVLs were linear and significantly differed among subjects, even those sharing an identical apoliporotein E genotype, ranging from .027 to .191 cc/year (S.D. = .022 cc/year), and were not affected by age or sex. rHVL, but not HV, at time of subject entry, was found to predict performance on the delayed recall measure of the Selective Reminder Task obtained 6 years after subject entry into study. Although the molecular events underlying rHVL are unclear, the significance of rHVL in subjects in their sixth and seventh decades of life for predicting age-related cognitive trajectories and whether changes in rHVLs foreshadow the development of MCI are the subject of ongoing study.


Subject(s)
Aging/pathology , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Hippocampus/pathology , Hippocampus/physiopathology , Models, Biological , Age Factors , Aged , Atrophy/pathology , Computer Simulation , Female , Humans , Linear Models , Male , Middle Aged , Reference Values
17.
Mol Cancer Ther ; 4(11): 1710-6, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16275992

ABSTRACT

Overexpression of the transcription factor E2F-1 induces apoptosis in a variety of carcinoma cells and inactivates murine double minute protein 2, a factor associated with poor prognosis in soft tissue sarcomas. We have shown previously that the double-stranded RNA-activated protein kinase PKR plays an important role in mediating this apoptotic response in carcinoma cells to E2F-1. We sought to evaluate the potential of E2F-1 gene therapy in soft tissue sarcomas and to study the involvement of PKR in the response to E2F-1 overexpression in mesenchymal cells. A replication-deficient adenovirus carrying the E2F-1 gene (Ad5E2F) was used to induce E2F-1 overexpression in the p53 mutated leiomyosarcoma cell line, SKLMS-1. Western blot analysis confirmed E2F-1 overexpression and up-regulation of the antiapoptotic factor Bcl-2 48 hours following infection with Ad5E2F. Apoptosis in Ad5E2F-treated cells was confirmed by fluorescence-activated cell sorting analysis and by poly(ADP-ribose) polymerase cleavage and DNA fragmentation assays. Vector-dependent up-regulation of PKR correlated with the amount of Ad5E2F-induced apoptosis. In vivo treatment of SKLMS-1 tumor-bearing BALB/c mice with intratumoral injections of Ad5E2F at a dose of 2 x 10(10) viral particles resulted in significant inhibition in tumor growth compared with control-treated animals (P < 0.016). Complete disappearance of all tumors was seen in two of seven mice in the Ad5E2F-treated animals. Immunohistochemical analysis of tumor specimens showed overexpression of E2F-1 and up-regulation of PKR in Ad5E2F-treated tumors. These findings show that adenovirus-mediated overexpression of E2F-1 results in up-regulation of PKR and significant growth suppression of leiomyosarcomas in vivo. Taken together, these data suggest that E2F-1 gene therapy and PKR modulation might be a promising treatment strategy for these tumors that are highly resistant to conventional therapies.


Subject(s)
Apoptosis , E2F1 Transcription Factor/genetics , Gene Expression Regulation, Neoplastic , Genetic Therapy/methods , Leiomyosarcoma/drug therapy , Leiomyosarcoma/pathology , Up-Regulation , eIF-2 Kinase/biosynthesis , Adenoviridae/genetics , Animals , Blotting, Western , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cell Separation , DNA Fragmentation , E2F1 Transcription Factor/therapeutic use , Flow Cytometry , Genetic Vectors , Immunohistochemistry , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Poly(ADP-ribose) Polymerases/metabolism , Prognosis , RNA, Double-Stranded/chemistry , Recombinant Proteins/genetics , Sarcoma/drug therapy , Time Factors , Tumor Suppressor Protein p53/metabolism
18.
Cancer ; 104(3): 479-90, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-15968686

ABSTRACT

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.


Subject(s)
Breast Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Carcinoma in Situ/diagnosis , Carcinoma in Situ/mortality , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/mortality , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Lymph Nodes/pathology , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Staging
20.
Cancer ; 104(1): 20-9, 2005 Jul 01.
Article in English | MEDLINE | ID: mdl-15912514

ABSTRACT

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.


Subject(s)
Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Mastectomy, Segmental , Neoplasm Recurrence, Local , Age Factors , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Radiotherapy, Adjuvant , Tamoxifen/therapeutic use , Time Factors , Treatment Outcome
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