bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome Evaluation in Pre-Trastuzumab Era between Different Breast Cancer Phenotypes: A Population-Based Study on Italian Women
Authors: Cortesi Laura , De Matteis Elisabetta , Cirilli Claudia , Marcheselli Luigi , Proietto Manuela , Federico Massimo 
Published: February 2018

Aims and background Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2–, Ki67 <14%), luminal B (ER and/or PgR/HER2–, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2–), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women. Methods and study design We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated. Results A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups. Conclusions In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.
Brain Metastases in Breast Cancer: Analysis of the Role of HER2 Status and Treatment in the Outcome of 94 Patients
Authors: Fokas Emmanouil , Henzel Martin , Hamm Klaus , Grund Steffen , Engenhart-Cabillic Rita 
Published: February 2018

Aims and background We investigated the impact of human epidermal growth factor receptor 2 (HER2) and prognostic factors in the outcome of patients with breast cancer that developed brain metastases. Methods The data from 94 patients who received multidisciplinary therapy from 2001 to 2007 were retrospectively reviewed. Patients were assigned according to their HER2 status, and overall survival and time to brain metastases recurrence/progression were evaluated. The prognostic value of age, presence of extracerebral metastases, recursive partitioning analysis class, hormone therapy, systemic therapy and trastuzumab was assessed. Results The median overall survival and time to brain disease progression were 7.1 and 6.5 months, respectively. HER2 positivity (P = 0.006), treatment with trastuzumab (P = 0.025), chemotherapy (P = 0.011) and recursive partitioning analysis class I-II (P <0.001) were associated with prolonged survival on univariate analysis. On multivariate analysis, only recursive partitioning analysis class I-II (P <0.001) and triple-negative disease (P = 0.04) remained significant for overall survival, whereas time to brain metastases progression was only associated with recursive partitioning analysis class I-II (P = 0.001). The time from the diagnosis of primary disease to brain metastasis was slightly shorter in the HER2+ patients than in HER2– patients (36 vs 39 months). Intensified local treatment of brain metastasis incorporating whole-brain radiotherapy and/or radiosurgery and neurosurgery did not affect survival. Patients with triple-negative disease presented a significantly lower survival than the rest of the cohort (4 vs 8 months; P = 0.012). Conclusions Recursive partitioning analysis class I-II was found to be the strongest independent predictive factor. Treatment with trastuzumab in HER2+ patients appeared to improve overall survival, probably due to the better control of systemic metastatic disease, but did not maintain significance in multivariate analysis. The dismal prognosis of patients with triple-negative breast cancer highlights the need to develop novel therapies to improve the poor survival.
Different methods of detaching adherent cells significantly affect the detection of TRAIL receptors
Authors: Zhang Bo , Shan Hong , Li Dan , Li Zheng-ran , Zhu Kang-shun , Jiang Zai-bo , Huang Ming-sheng 
Published: February 2018

Aims and background As a powerful technique allowing analysis of large numbers of cells, fluorescence-activated cell sorting (FACS) is used more and more widely. For FACS analysis, adherent cells are usually detached by trypsinization, followed by centrifugation and resuspension. However, trypsinization can cut off some receptors from the cell surface like fine scissors, which will affect the accuracy of FACS results. Though non-enzymatic methods such as citric saline buffer have been used to determine cell surface receptors, how much of the receptors is cut off by trypsinization has been rarely studied. This work aimed to investigate whether different methods of detaching adherent cells could affect the detection of cell surface receptors. Methods Human hepatocellular carcinoma cell lines (HepG2, Huh7 and Hep3B) were detached enzymatically with trypsin-EDTA solution or non-enzymatically with citric saline buffer, and then the receptors of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were detected by FACS analysis. Cell viability, cell cycle and apoptosis (sub-G1 fraction detected by FACS) of the trypsin-EDTA group and citric saline buffer group were also studied. Results Different methods of detaching adherent cells could significantly affect the detection of TRAIL receptors. Compared to the conventional trypsin-EDTA group, the non-enzymatic group showed a 3.42-fold increase in the mean fluorescence intensity index of DcR HepG2 and a 1.25-fold increase in DR Huh 7 (P <0.05). However, the viability, cell cycle and apoptosis of these cells were not affected. Conclusions Citric saline buffer might be recommended as the first choice to detach adherent cells for FACS analysis of cell surface receptors.
Up-regulation of p21WAF1/CIP1 by small activating RNA inhibits the in vitro and in vivo growth of pancreatic cancer cells
Authors: Zhang Zhiping , Wang Zhou , Liu Xiangyan , Wang Jie , Li Feng , Li Changling , Shan Baozhong 
Published: February 2018

Aims and background To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. Methods and study design A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. Results The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo. Conclusions dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.
Rare somatic mutation of pro-apoptotic BAX and BAK genes in common human cancers
Authors: Kim Min Sung , Kim Sung Soo , Yoo Nam Jin , Lee Sug Hyung 
Published: February 2018

Aims and background BAX and BAK are both pro-apoptotic Bcl-2 proteins and are essential for the pathway of intrinsic apoptosis. Apoptosis in cancer cells is frequently inactivated by somatic mutations. The aim of the study was to see whether somatic mutations of BAX and BAK genes are characteristics of common human cancers. Methods We analyzed somatic mutation of BAX and BAK genes in 47 gastric, 47 colorectal, 47 breast, 47 lung and 47 prostate carcinomas, and 47 acute leukemias by a polymerase chain reaction and single-strand conformation polymorphism assay. Results We identified BAX gene mutations in one colon (2.1%) and three gastric (6.4%) cancers. All of the mutations were frameshift mutations in the G8 repeat sequences and were detected in cancers with high microsatellite instability (36.4%). There was no evidence of BAX mutation in the other cancers, nor was somatic mutation of the BAK gene detected in the cancers. Conclusions Our data indicate that somatic mutation of BAX and BAK genes are rare in the common cancers (besides the cancers with high microsatellite instability) and suggest that neither BAX nor BAK mutation may causally be implicated in their tumorigenesis.
The “Don't Smoke in Our Home” Randomized Controlled Trial to Protect Children from Second-Hand Smoke Exposure at Home
Authors:   the Da noi non si fuma Study Group, Chellini Elisabetta , Gorini Giuseppe , Carreras Giulia 
Published: February 2018

Aims and background Increasing smoke-free homes is an important public health goal, but only few interventions have yielded positive results. The aim of the “Don't smoke in our home” trial was to evaluate a counseling intervention focused on promoting totally smoke-free homes and cars (TSFHC) delivered to women with children resident in four Tuscan towns. Methods and study design We used a two-group randomized controlled trial design. Participants were asked about their smoking habits and about restrictions on smoking in their homes and cars. All women received a self-help booklet promoting TSFHC, and 110 women randomized to the intervention also attended brief counseling on second-hand smoke exposure protection and received three gifts to remember the commitment to TSFHC. Follow-up was conducted by phone after four months. Results We recruited 218 women, 64 of whom had a university degree and 131 of whom were smokers; 62% reported smoking indoors and 58% in cars. Before the intervention, nonsmokers were more likely to report totally smoke-free homes (TSFH, 52%) and cars (TSFC, 53%) than smokers (26% and 17% respectively; P <0.001). Participants of the experimental arm had similar odds as controls of having implemented TSFH after the intervention, and nonsignificantly increased odds of having introduced TSFC (odds ratio [OR] 1.47; 95% confidence interval [CI] 0.69–3.11), particularly among smokers (OR 2.24, 95%CI 0.69–7.26). All participants independently of the study arm recorded significant increases of 12 and 15 percentage points in TSFH and TSFC, respectively. Few smokers quit smoking (7%), stopped smoking indoors (5%), and stopped smoking in cars (7%), with no differences between the intervention and control groups. Conclusions Adding brief counseling to written materials did not significantly increase TSFHC. However, delivering written materials only may produce modest but noteworthy TSFHC increases at the population level, even though the participants in the study did not represent a population-based sample, given the high proportion of highly educated women. Further studies are required to confirm these results.
Uncommon Breast Malignancies: Presentation Pattern, Prognostic Issue and Treatment Outcome in an Italian Single Institution Experience
Authors: Maria Regina Bareggi Claudia , Consonni Dario , Galassi Barbara , Gambini Donatella , Locatelli Elisa , Visintin Roberto , Runza Letterio , Giroda Massimo , Sfondrini Maria Silvia , Onida Francesco , Tomirotti Maurizio 
Published: February 2018

Aims and background Often neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series. Patients and methods Of 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome. Results Rare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12–0.62; P = 0.002). Conclusions According to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.
Plasma Osteopontin Level as a Diagnostic Marker of Hepatocellular Carcinoma in Patients with Radiological Evidence of Focal Hepatic Lesions
Authors: Khalil Ashraf , Elgedawy Jamalat , Faramawi Mohammed F , Elfert Ashraf , Salama Ibrahim , Abbass Ahmed , Elsaid Hala , Elsebaai Hatem 
Published: February 2018

Aims Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study. Subject and methods Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups. Results The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level. Conclusion Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.
Sentinel Lymph Node Biopsy in Breast Cancer: Review on Various Methodological Approaches
Authors: Zengel Baha , Yararbas Ulkem , Sirinocak Ahmet , Ozkok Guliz , Denecli Ali Galip , Postaci Hakan , Uslu Adam 
Published: February 2018

Aims and background Sentinel lymph node biopsy has been accepted as a standard procedure for early stage breast cancer. In this retrospective analysis, the results obtained with different methodological approaches using radiocolloid with or without blue dye were examined. Methods A total of 158 sentinel lymph node biopsies were performed in 152 patients. Group A (85 patients) underwent lymphatic mapping using a combination of periareolar intradermal radiocolloid and subareolar blue dye injections. Group B (73 patients) underwent only periareolar intradermal radiocolloid injection. One large tin colloid and two small radiocolloids (nanocolloid of serum albumin -NC- and colloidal rhenium sulphide -CS-) were used. Results Successful lymphatic mapping was attained in 157 of 158 procedures (99.4%). Radiocolloids localized sentinel lymph nodes in 99.4% and blue dye in 75.3% of the cases. The number of sentinel lymph nodes removed was greater in nanocolloid and colloidal rhenium sulphide groups ( P ≤0.05). Among 60 metastatic sentinel lymph nodes, frozen section analysis using hematoxylin and eosin staining failed to detect 1 macro- and 10 micrometastasis. Radiocolloid uptake was higher in sentinel lymph nodes accumulating blue dye (1643 ± 3216 counts/10 sec vs 526 ± 1284 counts/10 sec, P <0.001). Higher count rates were obtained by using larger sized colloids (median and interquartile range: tin colloid, 2050 and 4548; nanocolloid, 835 and 1799; colloidal rhenium sulphide, 996 and 2079; P = 0.01). Only 2 extra-axillary sentinel lymph nodes were visualized using periareolar intradermal injection modality. Conclusions Radiocolloids were more successful than blue dye in sentinel lymph node detection. More sentinel lymph nodes were harvested with small colloids, but different sized radiocolloids were similarly successful. Sentinel lymph nodes having higher radiocolloid uptake tended to accumulate blue dye more frequently. Sentinel lymph nodes manifested higher count rates when a larger colloid was used. Frozen section was very successful in detecting macrometastatic disease in sentinel lymph nodes, but the technique failed in most of the micrometastates.
Once-Weekly Stereotactic Radiotherapy for Patients with Oligometastases: Compliance and Preliminary Efficacy
Authors: Corvò Renzo , Lamanna Giorgio , Vagge Stefano , Belgioia Liliana , Bosetti Davide , Aloi Deborah , Timon Giorgia , Bacigalupo Almalina 
Published: February 2018

Aims and background This retrospective analysis reports the outcomes obtained with an original once-weekly stereotactic radiotherapy fractionation given to patients affected by evolving oligometastases from different solid malignancies. Methods From 2009 to 2011, patients with symptomatic and/or evolving oligometastases were submitted to a median 5-fraction cycle of stereotactic radiotherapy of one fraction per week in order to exploit a radiobiological rationale designed to increase the therapeutic index. Individual fractionation was mainly planned according to patient performance status, oligometastasis size and site, and record of previous irradiation in the same site. Results Thirty-six patients in stage IV UICC-TNM affected by oligometastases were treated with image-guided intensity-modulated stereotactic tomotherapy with a single weekly radiation. Median age was 70 years (range, 34–89). The median weekly single dose, number of fractions and overall total radiation dose were 7 Gy, 5 fractions and 35 Gy, respectively. Thirty-five (97%) patients completed the treatment schedule. No patient suffered mild or severe radiation-related side effects. Twenty-one (87%) of 24 patients with local pain had complete symptomatic response within 30 days following the end of radiotherapy. Local control assessed at imaging after stereotactic radiotherapy was evidenced in 30 (83%) patients. Median time to response after the end of radiotherapy was 40 days. Conclusions The original radiotherapy regimen delivering only a single stereotactic dose per week seems to be highly feasible with an interesting high efficacy rate in patients with oligometastases from different solid tumors. Overall, the once-weekly treatment was very compliant in an advanced cancer stage especially for elderly and frail patients.
Predictive Factors for Child-Pugh Score Elevation in Hepatocellular Carcinoma Patients Treated with Conformal Radiation Therapy: Dose-Volume Histogram Analysis
Authors: Yu Jeong Il , Park Hee Chul , Lim Do Hoon , Park Woo Yoon 
Published: February 2018

Aims and background We designed the study to identify the clinical and dose-volumetric parameters associated with the risk of Child-Pugh score elevation in hepatocellular carcinoma patients treated with conformal radiation therapy. Methods and study design All 161 hepatocellular carcinoma patients in the study underwent 4D-computed tomography simulation, and a dose-volume histogram was generated after radiotherapy planning. Patients who had an elevated Child-Pugh (e-CP) score of 2 or more without progressive disease within 3 months were defined as e-CP positive. Results Twenty-six of 142 patients without progressive disease were e-CP positive. Pretreatment Child-Pugh class, further treatment within 30 days of radiotherapy, lymph node metastasis, mean liver dose, V20 Gy, V25 Gy, and V30 Gy were significantly correlated with e-CP positivity. The e-CP developed in 13 of 106 patients (12.3%) with V30 Gy of ≤28.1% and in 13 of 36 patients (36.1%) with V30 Gy >28.1% ( P = 0.001). Conclusions Our data demonstrate that mean liver dose, V10 Gy, V20 Gy, V25 Gy, and V30 Gy are independent dose-volumetric predictors for e-CP positivity in hepatocellular carcinoma patients treated with conformal radiation therapy. V30 Gy should be limited to less than 28.1% to minimize the risk of e-CP.
Suspecting Malignancy in Endometrial Polyps: Value of Hysteroscopy
Authors: Daniele Alberto , Ferrero Annamaria , Maggiorotto Furio , Perrini Gaetano , Volpi Eugenio , Sismondi Piero 
Published: February 2018

Aims and background Hysteroscopic polypectomy is the gold standard to treat endometrial polyps and obtain specimens for histological evaluation. There is continuing debate as to when to offer hysteroscopic polypectomy, especially in asymptomatic women with incidental lesions. The aims of this study were to assess the accuracy of hysteroscopy and Vabra sampling in diagnosing atypical hyperplasia and cancer growing on the surface of endometrial polyps and to investigate the association between atypical endometrial polyps and some potential clinical risk factors. Methods and study design This was a retrospective study. We assessed 1039 hysteroscopies and we identified 345 women with endometrial polyps. All patients with endometrial polyps underwent hysteroscopic polypectomy. Data about age, menopausal status, abnormal uterine bleeding (AUB), hormone replacement therapy and tamoxifen use were collected. Hysteroscopic, histological and clinical data were analyzed. Results The incidence of endometrial hyperplasia or cancer growing on the surface of endometrial polyps was significantly low (1.7%). Hysteroscopy correctly excluded (negative predictive value: 100%) and accurately predicted (positive predictive value: 85.7%) preneoplastic or neoplastic lesions growing within the epithelial layer of endometrial polyps. Vabra sampling was inadequate for the histological diagnosis in 38.5% of cases. Age over 60 years and postmenopausal AUB were associated with an 8.3-fold ( P = 0.022) and 8.8-fold ( P = 0.020) increased risk, respectively, of preneoplastic and neoplastic lesions growing on the surface of endometrial polyps. Conclusions Diagnostic hysteroscopy is a good tool to predict malignancy of the epithelial layer of endometrial polyps. Age over 60 years and AUB are associated with an increased risk of malignant polyps. Few suspicious endometrial polyps should undergo surgical resection.