Association of ABO and Rh blood groups with breast cancer

ObjectivesThe aim of this study was to determine the association of “ABO” and “Rhesus” blood groups with incidence of breast cancer.MethodsIn this study, we identified 70 research documents from data based search engines including “PubMed”, “ISI-Web of Knowledge”, “Embase” and “Google Scholar”. The research papers were selected by using the primary key-terms including “ABO blood type”, “Rhesus” blood type and “breast cancer”. The research documents in which “ABO” and “Rhesus” blood types and breast cancer was debated were included. After screening, we reviewed 32 papers and finally we selected 25 research papers which met the inclusion criteria and remaining documents were excluded.ResultsBlood group “A” has high incidence of breast cancer (45.88%), blood group “O” has (31.69%); “B” (16.16%) and blood group “AB” has (6.27%) incidence of breast cancer. Blood group “A” has highest and blood group “AB” has least association with breast cancer. Furthermore, “Rhesus +ve” blood group has high incidence of breast cancer (88.31%) and “Rhesus –ve” blood group has least association with breast cancer (11.68%).ConclusionBlood group “A” and “Rhesus +ve” have high risk of breast cancer, while blood type “AB” and “Rhesus –ve” are at low peril of breast cancer. Physicians should carefully monitor the females with blood group “A” and “Rh +ve” as these females are more prone to develop breast cancer. To reduce breast cancer incidence and its burden, preventive and screening programs for breast cancer especially in young women are highly recommended.     

~(131)I-Herceptin对HER2过表达乳腺癌细胞Bcl-xL表达的影响

目的:探讨131I-Herceptin对HER2过表达乳腺癌细胞Bcl-x L表达的影响。方法:采用Iodogen法制备131I-Herceptin,超滤法纯化后测定其标记率、放射化学纯度和免疫结合率。通过免疫荧光法检测乳腺癌细胞表面HER2表达水平。131I(4.625 MBq/m L)、Herceptin(125μg/m L)及131I-Herceptin(4.625 MBq/m L)干预乳腺癌BT474细胞后,Western blot检测细胞中Bcl-x L的表达。结果:131I-Herceptin的标记率、放射化学纯度和免疫结合率分别为(89.71±2.93)%、(91.80±1.43)%和(58.84±3.35)%。BT474细胞膜表面HER2表达水平明显高于MDA-MB-231细胞。Herceptin、131I-Herceptin组BT474细胞内Bcl-x L表达水平明显低于对照组及131I组(均P0.01),而Herceptin与131I-Herceptin组之间细胞内Bcl-x L含量差异无统计学意义(P0.05)。结论:131I-Herceptin保留Herceptin对HER2过表达乳腺癌细胞Bcl-x L表达的抑制作用并促进细胞凋亡,进而与131I产生协同作用,较Herceptin更有效地杀伤HER2过表达乳腺癌细胞。     

Dosimetric evaluation of Gafchromic EBT2 film for breast intraoperative electron radiotherapy verification

PurposeQuality assurance (QA) is one of the most important issues that should be addressed for intraoperative electron radiotherapy (IOERT), which is not benefiting from image-based treatment planning system. The aim of this study is to evaluate the dosimetric characteristics of Gafchromic EBT2 film for breast IOERT QA procedure.MethodsDue to the fact that some dedicated accelerators are being used for IOERT, dependence of the film response to energy, field size, dose rate and incidence angle of electron beam from the LIAC IOERT accelerator was studied. Then, film response curve to breast IOERT doses was obtained and its accuracy was evaluated and justified through comparison to the results of ionometric dosimetry.ResultsThe results of this study indicated that there are no significant differences between the film responses at different energies of 6, 8, 10 and 12 MeV (P-value = 0.99). Similarly, no field size dependency was found when evaluating the response of the film to different field sizes ranging from 4 to 10 cm (P-value = 0.94). Film response was found to be independent of the dose rate of intraoperative electron beam (P-value = 0.12). Film response variations with changing the beam incidence angle were not significant (P-value > 0.8). Calibration curve at the dose range of 8–24 Gy had an acceptable accuracy. The difference between the results of film dosimetry and ionometric dosimetry was around 5% which was in agreement with the results of dose uncertainty estimation.ConclusionThe EBT2 film was found to be a potentially appropriate tool for breast IOERT verification.     

Tetrahydroindolocarbazoles (THICZs) as new class of urokinase (uPA) inhibitors: Synthesis,anticancer evaluation,DNA-damage determination,and molecular modelling study

Tetrahydroindolocarbazoles (THICZs) with versatile substituents, have been designed, synthesized, structure characterized, then investigated for their in-vitro anticancer screening, urokinase inhibition (uPA) evaluated, DNA-damage determination was further explored. Compounds 5, 8, 10 and 17 displayed the most promising antitumor activities against the breast cancer cell line as compared to the standard drug, doxorubicin with IC₅₀ = 5.24 ± 0.37, 4.00 ± 0.52, 7.20 ± 0.90 and 9.60 ± 1.10 µg/ml (versus 3.30 ± 0.48 µg/ml for doxorubicin). Compounds 5, 8, 10 and 17 represents the most significant uPA inhibitors of our study with IC₅₀ of 3.80, 2.70. 4.75, 10.80 (ng/ml) respectively. The expression levels of CDKN2A gene were decreased in 8, 10 and 17 cell lines as compared to those in positive control samples. Cell lines treated with 5, 8, 10 and 17 clearly observed a high score of damaged DNA cells. A deeper examination revealed that our hetroaromatics showed an extensive hydrogen bonding interactions that is required in the S pocket which is important for activity Arg 217, Gly 219, Gly 216, Lys 143 and Ser 190. So we present THICZs as promising uPA inhibitors expected as significant promise for further development as anti-invasiveness drugs.     

microRNA-1298 inhibits the malignant behaviors of breast cancer cells via targeting ADAM9

MicroRNAs (miRNAs) regulate the progression of human malignancy by targeting oncogenes or tumor suppressors, which are 12 promising targets for cancer treatment. Increasing evidence has suggested the aberrant expression and tumor-suppressive function of miR-1298 in cancers, however, the regulatory mechanism of miR-1298 in breast cancer (BC) remains unclear. Here, our findings showed that miR-1298 was down-regulated in BC tissues and cell lines. Lower level of miR-1298 was significantly correlated with the advanced progression of BC patients. Experimental study showed that overexpression of miR-1298 inhibited the proliferation, induced apoptosis and cell cycle arrest in BC cells. The in vivo xenograft mice model showed that highly expressed miR-1298 significantly reduced the tumor growth and metastasis. Further mechanism analysis revealed that miR-1298 bound the 3′-untranslated region (UTR) of a disintegrin and metalloproteinase 9 domain (ADAM9) and suppressed the expression of ADAM9 in BC cells. ADAM9 was overexpressed in BC tissues and inversely correlated with miR-1298. Down-regulation of ADAM9 induced apoptosis and cell cycle arrest of BC cells. Moreover, ectopic expression of ADAM9 by transiently transfecting with vector encoding the full coding sequence of ADAM9 attenuated the inhibitory effects of miR-1298 on the proliferation and cell cycle progression of BC cells. Collectively, our results illustrated that miR-1298 played a suppressive role in regulating the phenotype of BC cells through directly repressing ADAM9, suggesting the potential application of miR-1298 in the therapy of BC.     

Activation of the pro-migratory bone morphogenetic protein receptor 1B gene in human MDA-MB-468 triple-negative breast cancer cells that over-express CYP2J2

Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control] ≥2). From gene ontology pathway analysis bone morphogenetic protein (BMP) receptor 1B (BMPR1B) emerged as an important upregulated gene in MDA-2J2 cells. Addition of the BMPR1B ligand BMP2 stimulated the migration of MDA-2J2 cells, but not MDA-CTL cells, from 3D-matrigel droplets. Migration of MDA-2J2 cells was prevented by the BMPR antagonist dorsomorphin. These findings indicate that over-expression of CYP2J2 in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may contribute to increased migration. Targeting BMPR1B may be a novel approach to inhibit the metastatic activity of breast cancers that contain high levels of CYP2J2.     

Phosphorylation of Cdc42 Effector Protein-4 (CEP4) by Protein Kinase C Promotes Motility of Human Breast Cells

Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. The significance of phosphorylated CEP4 to PKC-stimulated motility of MCF-10A cells was evaluated. Single site mutants at Ser residues embedded in potential PKC consensus sites (Ser¹⁸, Ser⁷⁷, Ser⁸⁰, and Ser⁸⁶) were individually replaced with Asp residues to simulate phosphorylation. Following expression in weakly motile MCF-10A cells, the S18D and S80D mutants each promoted increased motility, and the double mutant (S18D/S80D) produced a stronger effect. MS/MS analysis verified that Ser¹⁸ and Ser⁸⁰ were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes). In contrast, the phosphorylation-resistant double mutant S18A/S80A-CEP4 blocked CEP4 phosphorylation and inhibited motility of MCF-10A cells that had been stimulated with PKC activator diacylglycerol lactone. In view of the dissociation of phospho-CEP4 from Cdc42, intracellular binding partners were explored by expressing each CEP4 double mutant from a tandem affinity purification vector followed by affinity chromatography, SDS-PAGE, and identification of protein bands evident only with S18D/S80D-CEP4. One binding partner was identified as tumor endothelial marker-4 (TEM4; ARHGEF17), a guanine nucleotide exchange factor that is involved in migration. In motile cells expressing S18D/S80D-CEP4, knockdown of TEM4 inhibited both Rac activation and motility. These findings support a model in which PKC-mediated phosphorylation of CEP4 at Ser¹⁸ and Ser⁸⁰ causes its dissociation from Cdc42, thereby increasing its affinity for TEM4 and producing Rac activation, filopodium formation, and cell motility.     

Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene

Epidemiological evidence has suggested an association between meat consumption and the risk of breast cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, has been implicated in the aetiology of breast cancer and has been shown to induce tumour formation in rodent mammary glands. In addition, polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) which has also been shown to induce tumour formation at a number of sites in rodents including the breast, are produced during the cooking of meat through the pyrolysis of fats. The aim of this study was to examine the bioavailability of these compounds to human breast tissue and their ability to bind to DNA to form DNA adducts. Patients undergoing breast surgery at York District Hospital were orally administered prior to surgery a capsule containing 20 μg of ¹⁴C PhIP (182 kBq, specific activity 2.05 GBq/mmol) or 5 μg of ¹⁴C B[a]P (36 kBq, specific activity 1.81 GBq/mmol). At surgery, normal and tumour breast tissue was resected and tissue concentrations of carcinogen measured by liquid scintillation counting and DNA adduct levels by accelerator mass spectrometry (AMS) were subsequently determined. It was found that both ¹⁴C PhIP and ¹⁴C B[a]P were able to reach the target organ where they had the ability to form DNA adducts. The level of adducts ranged from 26.22–477.35 and 6.61–208.38 adducts/10¹² nucleotides following administration of ¹⁴C PhIP and ¹⁴C B[a]P, respectively, with no significant difference observed between levels in normal or tumour tissue. In addition, the data obtained in this study were comparable to adduct levels previously found in colon samples following administration of the same compounds to individuals undergoing colorectal surgery. This is the first report that these two carcinogens bind to human breast DNA after administration of a defined low dose.     

Radiation techniques used in patients with breast cancer: Results of a survey in Spain

AimTo evaluate the resources and techniques used in the irradiation of patients with breast cancer after lumpectomy or mastectomy and the status of implementation of new techniques and therapeutic schedules in our country.BackgroundThe demand for cancer care has increased among the Spanish population, as long as cancer treatment innovations have proliferated. Radiation therapy in breast cancer has evolved exponentially in recent years with the implementation of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, image guided radiotherapy and hypofractionation.Material and MethodsAn original survey questionnaire was sent to institutions participating in the SEOR-Mama group (GEORM). In total, the standards of practice in 969 patients with breast cancer after surgery were evaluated.ResultsThe response rate was 70% (28/40 centers). In 98.5% of cases 3D conformal treatment was used. All the institutions employed CT-based planning treatment. Boost was performed in 56.4% of patients: electrons in 59.8%, photons in 23.7% and HDR brachytherapy in 8.8%. Fractionation was standard in 93.1% of patients. Supine position was the most frequent. Only 3 centers used prone position. The common organs of risk delimited were: homolateral lung (80.8%) and heart (80.8%). In 84% histograms were used. An 80.8% of the centers used isocentric technique. In 62.5% asymmetric fields were employed. CTV was delimited in 46.2%, PTV in 65% and both in 38.5%. A 65% of the centers checked with portal films. IMRT and hypofractionation were used in 1% and in 5.5% respectively.ConclusionIn most of centers, 3D conformal treatment and CT-based planning treatment were used. IMRT and hypofractionation are currently poorly implemented in Spain.