- Neoadjuvant Radiotherapy: Changing the Treatment Sequence to Allow Immediate Free Autologous Breast Reconstruction. [Journal Article]
- JRJ Reconstr Microsurg 2018 Jun 16
- CONCLUSIONS: From our experience, this treatment sequence allows patients to have an immediate gold standard reconstruction without an increase in surgical morbidity. It affords the benefits of IBR without concern in delaying adjuvant therapy and appears to be safe from an oncological perspective.
- Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma. [Journal Article]
- EJEur J Med Chem 2018 Jun 11; 155:503-515
- Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour...
Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour cells. Three analogues of 3j were designed and synthesized keeping in view the structural requirements of this compound. Almost all the tested compounds displayed considerable cytotoxicity. However, 8a, one of the 3j analogues, was shown to be highly selective and cytotoxic, especially for breast carcinoma cells (MCF-7) (IC50 = 3.9 μM). Furthermore, 8a caused DNA damage, inhibited cell proliferation, was able to arrest cell cycle in S phase, and induced cell death by apoptosis in human breast carcinoma cells. Moreover, predictions of pharmacokinetic properties showed that 8a may present good absorption and permeation characteristics for oral administration. Overall, the current study established 8a as a potential drug prototype to be employed as a DNA interactive cytotoxic agent for the treatment of breast cancer.
- Synthesis and biological evaluation of new coumarins bearing 2,4-diaminothiazole-5-carbonyl moiety. [Journal Article]
- EJEur J Med Chem 2018 Jun 07; 155:483-491
- A series of new coumarin-containing compounds 3a-l and 4a-c was designed and synthesized based on the chalcone-type 4-amino-5-cinnamoylthiazole scaffold 2, and screened for their in vitro anticancer ...
A series of new coumarin-containing compounds 3a-l and 4a-c was designed and synthesized based on the chalcone-type 4-amino-5-cinnamoylthiazole scaffold 2, and screened for their in vitro anticancer and antioxidant activities. Representatively, the 2-thiomorpholinothiazole derivative 3k with IC50 values of 7.5-16.9 μg/ml demonstrated good cytotoxic effects against tested cell lines MCF-7, HepG2 and SW480. Further investigation by flow cytometric analysis confirmed that this compound induces apoptotic cell death in MCF-7 cells and cause G1-phase arrest in the cell cycle. Moreover, most of compounds had intrinsic potential for radical scavenging activity and ferric-reducing power as investigated by DPPH and FRAP assays.
- Nitroxide radical-containing nanoparticles attenuate tumorigenic potential of triple negative breast cancer. [Journal Article]
- BBiomaterials 2018 May 26; 178:48-62
- The critical importance of reactive oxygen species (ROS) as oncogene activators and essential secondary messengers in cancer cell survival have been widely reported. Since oxidative stress has been i...
The critical importance of reactive oxygen species (ROS) as oncogene activators and essential secondary messengers in cancer cell survival have been widely reported. Since oxidative stress has been implicated as being pivotal in various cancers, antioxidant therapy seems an apt strategy to abrogate ROS-mediated cellular processes to attenuate cancers. We therefore synthesized ROS scavenging nitroxide radical-containing nanoparticles (RNPs); pH insensitive RNPO and pH sensitive RNPN, to impede the proliferative and metastatic characteristics of the triple negative breast cancer cell line, MDA-MB-231, both in vitro and in vivo. RNPs significantly curtailed the proliferative and clonogenic potential of MDA-MB-231 and MCF-7 cell lines. Inhibition of ROS-mediated migratory and invasive characteristics of MDA-MB-231, via down regulation of NF-κB and MMP-2, was also confirmed. Furthermore, a significant anti-tumor and anti-metastatic potential of RNPs was observed in an MDA-MB-231 mouse xenograft model. Such tumoricidal effects of RNPs were attained with negligible adverse effects, compared to conventional low molecular weight antioxidants, TEMPOL. Thus, the tumoricidal effects of RNPs are suggestive of insights on precedence of nanoparticle-based therapeutics over current low molecular weight antioxidants to curtail ROS-induced tumorigenesis of various cancers.
- Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial. [Journal Article]
- BONEBone 2018 Jun 13
- CONCLUSIONS: In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment.
- Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation. [Journal Article]
- GENEGene 2018 Jun 13
- Breast cancer is the most common malignant tumor in women worldwide. Breast tumors mostly exhibit aberrant gene expression and DNA hypermethylation patterns that predispose the disease. Understanding...
Breast cancer is the most common malignant tumor in women worldwide. Breast tumors mostly exhibit aberrant gene expression and DNA hypermethylation patterns that predispose the disease. Understanding the genetic and epigenetic factors that contribute to breast cancer development is important to identify novel diagnostic and prognostic markers. SCARA5: Scavenger receptor class A, member 5; is a member of the scavenger receptor family located on chromosome 8p21 which is a frequently deleted region in human cancers. SCARA5 has been identified as a candidate tumor suppressor gene in various kinds of cancer. However, its role in breast cancer remains unclear. Therefore, in the present study SCARA5 expression levels in breast tumors and matched noncancerous tissue samples from 77 patients were analyzed by qRT-PCR and the expression levels were correlated with the methylation level of SCARA5 gene promoter. We found that SCARA5 expression was significantly decreased in tumors (92.2%) compared to non-cancerous tissue samples and this down-regulation was associated with hypermethylation of the promoter (p < 0.001). A significant correlation was also detected between SCARA5 expression and the histological grade of the breast tumors (p = 0.017). Taken together, our results indicate that SCARA5 may play an important role in tumorigenesis of breast cancer via promoter methylation.
- Design and development of PEGylated liposomal formulation of HER2 blocker Lapatinib for enhanced anticancer activity and diminshed cardiotoxicity. [Journal Article]
- BBBiochem Biophys Res Commun 2018 Jun 13
- Breast cancer is most frequently diagnosed cancer and fifth leading cause of death in women. About 20-30% of all breast cancers overexpress HER2/neu receptors. Lapatinib is a dual tyrosin kinase inhi...
Breast cancer is most frequently diagnosed cancer and fifth leading cause of death in women. About 20-30% of all breast cancers overexpress HER2/neu receptors. Lapatinib is a dual tyrosin kinase inhibitor of EGFR and HER2. It exhibits its anticancer effect via blocking intracellular domain of HER2 receptor in breast cancer. Lapatinib belongs to class II of BSC classification due to its poor solubility restricting its clinical application. Due to presence of HER2 receptor on cardiomyocytes, it is associated with generation of cardiotoxicity. The present study was aimed to design a PEGylated liposomal formulation of Lapatinib and evaluate its anticancer potential. Lapatinib liposomes were prepared using lipid layer hydration method and its characterization was done by determining its particle size, zeta potential, entrapment efficiency and in vitro release profiling. The anti-tumor activity of PEGylated liposomal formulation was evaluated in xenografted tumor induced by MDA-MB-453 breast cancer cells in chick embryos. The anti-tumor effect of lapatinib was enhanced by its PEGylated liposomal preparation as it led to the reduction in tumor size to a greater extent compared to the embryos treated with free lapatinib. Flowcytometric analysis and immunofluroscence study using cleaved PARP antibody demonstrated the enhaced apoptotic potential of PEGylated liposomes of lapatonib. SGOT levels, marker for cardiotoxicity and hepatotoxicity, significantly decreased in serum of embryos treated with PEGylated liposmes of lapatinib compared to free drug treated embryos. Hence, the PEGylated liposomal formulation of lapatininb can be used as a therapeutic strategy against HER2 positive breast cancer either alone or in combination with conventional anticancer agents and hormonal therapies.
- Glycyrrhizin has a high likelihood to be a victim of drug-drug interactions mediated by hepatic OATP1B1/1B3. [Journal Article]
- BJBr J Pharmacol 2018 Jun 16
- CONCLUSIONS: Transporter-mediated hepatobiliary excretion governs glycyrrhizin's elimination and pharmacokinetics. Understanding glycyrrhizin's potential drug-drug interactions on OATP1B1/1B3 is expected to enhance success of glycyrrhizin-including combination drug therapies of liver diseases.
- Distribution of 21-Gene Recurrence Scores in Male Breast Cancer in the United States. [Journal Article]
- ASAnn Surg Oncol 2018 Jun 15
- CONCLUSIONS: Using a large population-based dataset, we found that compared with women, men were significantly more likely to have high-risk RS. Grade III and PR-negative BC were significantly associated with high-risk RS. Higher RS in men correlated with increased chemotherapy utilization.
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- Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy. [Journal Article]
- MOMed Oncol 2018 Jun 16; 35(7):107
- The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients (≥ 65 years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-pos...
The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients (≥ 65 years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-positive breast cancer patients given hypofractionated whole-breast radiotherapy from June 2009 to September 2016. Baseline comorbidities considered in the hypertension-augmented Charlson Comorbidity Index (hCCI) were retrospectively retrieved. Total hCCI scores were classified as no comorbidity (hCCI = 0), low burden of comorbidity (hCCI = 1), and high burden of comorbidity (hCCI ≥ 2). Competing risk analysis was used to estimate the 5-year cumulative incidence of HT discontinuation. Fine and Gray models were used to estimate the adjusted subhazard ratio (SHR) of HT discontinuation by hCCI score. HT was initially prescribed for 85.6% of patients and almost all of them (468/471) took it for at least one month. It was subsequently discontinued by 45 patients (9.6%), for an overall 5-year cumulative incidence of 11.7%. The 5-year cumulative incidence of HT discontinuation rose from 3.9% in the youngest age group (65-69 years) to 23.3% in the oldest (≥ 80 years) (p = 0.005). Baseline comorbidity had some effect on the likelihood of discontinuing HT, but only among patients with a low burden of comorbidity (hCCI = 1, SHR 2.00, 95%CI 0.95-4.20). Adherence to HT was better in our sample than in the literature, probably because patients were selected and motivated to continue HT. This confirms the importance of communication with patients to improve adherence to HT. We confirmed the association between HT discontinuation and older age, while comorbidity had a limited influence.