bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammosphere Culture of Established Cell Lines Does Not Enrich for a More Tumorigenic Breast Cancer Stem Cell Population.
Authors: Iorns E. , Clarke J. , Dean S. , Lippman M. 
Published: December 2010

Abstract
Background:The cancer stem cell model suggests that tumors arise from and are maintained by a relatively small proportion of cells, termed cancer stem cells. According to this model, only these cells have the capacity for self-renewal and the ability to repopulate the tumor bulk by giving rise to the phenotypically heterogeneous populations of cells that comprise the primary tumor. Evidence to support the cancer stem cell model has been provided by isolation of subpopulations of cells on the basis of differential expression of cell surface markers, followed by functional transplantation into animal models. These studies reveal that only a small subset of CD44+/CD24-/low cancer cells retain the ability to form new tumors after transplantation in immunodeficient mice, consistent with the cancer stem cell model. These results indicate that it may be necessary to target and eliminate cancer stem cells in order to eradicate tumors.Material and Methods:Previous studies have suggested that only breast stem cells have the capacity to proliferate in suspension as spherical colonies termed mammospheres, and that mammosphere derived breast cancer cells are CD44+/CD24-/low and able to form tumors that reproduce the heterogeneity of the original primary tumor when injected into the mammary fat pad of immunodeficient mice. This indicates that mammospheres are comprised of breast cancer stem cells. To identify and characterize breast cancer stem cells more completely, the mammosphere culture system was used to isolate and propagate breast cancer stem cells from three basal breast cancer cell lines (BT549, MDA231, MDA436) and three luminal breast cancer cell lines (MCF7, SKBR3, T47D). The tumorigenicity of the cultured mammospheres and parental cell lines was examined using dilution studies in immunodeficient mice and gene expression profiles were studied by microarray analysis.Results and Discussion:No significant differences in tumorigenicity were observed between breast cancer cells cultured as mammospheres versus standard culture conditions. Furthermore, no consistent differences in gene expression profiles were observed between mammosphere and parental cells across the panel of cancer cell lines. These results suggest that mammosphere culture is not capable of significantly enriching for a more tumorigenic breast cancer stem cell population from established breast cancer cell lines. This may indicate that cancer subpopulations that exist in primary tumors are lost during the long term culture of breast cancer cell lines and that these systems may not be a suitable model for breast cancer stem cell studies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 502.
Pathological and Patient Factors Affecting the Accuracy of Ultrasound Combined with Fine Needle Aspiration Cytology in Pre-Operative Staging of the Axilla in Breast Cancer.
Authors: Hogan B. , Peter M. , Langlands F. , White J. , Dall B. , Horgan K. 
Published: December 2010

Abstract
Introduction:Ultrasound combined with fine needle aspiration cytology is effective in pre-operative staging of the axilla in breast cancer. Accurate pre-operative diagnosis of lymph node metastases allows for a one stage axillary operation and may also influence decisions regarding neo-adjuvant chemotherapy and breast reconstruction. The aim of this study is to identify pathological and patient factors that influence the accuracy of ultrasound and FNAC in determining the status of the axilla pre-operatively.Methods:Three hundred patients with primary operable invasive breast cancer had an axillary ultrasound pre-operatively. If the ultrasound was normal the patient was offered a sentinel node biopsy. If it identified equivocal or pathological nodes a fine needle aspirate cytology was performed. If the cytology was malignant then an axillary node clearance was performed.Results:Ultrasound combined with FNAC correctly determined the status of the axilla pre-operatively in 78% of cases. Sensitivity for the detection of metastases was 32% with 100% specificity. Factors affecting the accuracy of ultrasound and FNAC were the pathological size of tumour (p&lt;0.05) and the size of the metastases (p&lt;0.05). Age of the patient, pathological grade and type of tumour did not significantly affect the accuracy of the procedure.Conclusion:Ultrasound combined with fine needle aspirate cytology can be used effectively to determine the status of the axilla pre-operatively. All patients regardless of age or their particular tumour characteristics should be offered this procedure pre-operatively.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5020.
Utility of Breast CT in the Management of Breast Cancer – Results from a Prospective Multi-Institutional Study.
Authors: Akashi-Tanaka S. , Sato N. , Ohsumi S. , Kimijima I. , Inaji H. , Teramoto S. , Akiyama F. 
Published: December 2010

Abstract
Background:In order to obtain negative margins after breast conserving surgery (BCS), even repeated surgery is widely accepted. Before surgery, it is important to conduct a precise assessment of the extent of the breast cancer so that each patient can receive individualized surgery. To evaluate the utility of breast computed tomography (CT) as a tool to manage BCS, a multi-institutional prospective study was conducted in Japan.Patients and Methods:Patients were eligible to participate in this study if they had histologically proven breast cancer and were determined to be BCS candidates based on palpation, mammography (MMG) and ultrasonography (US). Written informed consent was obtained from each patient. First, the surgeon marked the line of planned excision on the skin using information from the MMG and US. Next, an expired angiographic catheter was placed on the mark to show the original surgical margin on the CT image. Breast CT was scanned 60 seconds after the bolus injection of the contrast material in the supine surgical position. The surgeon determined the extent of surgery based on the breast CT results. Surgical specimens were serially sectioned in 5-mm slices.Results:Three hundred and two patients were enrolled in this study. The CT scanners used in this study varied from a single helical CT to a 64-row multidetector CT. The results of the breast CT changed the extent of resection in 14.7% of patients. Among the 5 patients who were recommended to undergo a mastectomy, 4 patients had multicentric tumors pathologically and 1 patient had a widely spread intraductal component. The other patients were recommended to have a quadrantectomy based on the extent of breast cancer that was visualized by CT. Three patients (1%) who required conversion from a lumpectomy to quadrantectomy resulted in overexcision. In short, breast CT correctly changed the extent of surgery in 13.7% of the examined patients.Conclusion:This prospective study suggested that breast CT is useful for hospitals equipped with any type of CT and can be used to provide patients with individualized surgery.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5021.
Optimizing Breast Cancer Follow-Up: Diagnostic Value and Costs of Additional Routine Breast Ultrasound.
Authors: Wojcinski S. , Hirschauer E. , Degenhardt F. , Schmidt W. 
Published: December 2010

Abstract
Background: Standard means in breast cancer follow-up include clinical examination and mammography for the detection of local recurrences. Additional test will only be conducted if there are unclear or suspicious findings. Ultrasound has not yet been established as a routine method for breast cancer follow-up care. Our study evaluates the diagnostic efficacy of breast ultrasound in detecting occult malignancies. Moreover, we analyzed the effect of false positive findings resulting in additional examinations and biopsies, and we conducted a benefit-cost-analysis and a questioning of the affected patients.Materials and Methods: A total of 879 eligible patients who were seen at the University Hospital of Saarland for the purpose of breast cancer follow-up were recruited between October 2004 and January 2006. All patients received clinical examination and mammography and were then divided into 2 groups. Group 1 (n=703) were clinically and mammographically asymptomatic patients. Group 2 (n=176) had abnormalities either in palpation or mammography. All patients received additional ultrasound in order to detect occult malignancies. Both groups were analyzed with respect to the diagnostic value of additional ultrasound, the rate of additional examinations and biopsies, the extra costs and the individual stress as experienced by the patient.Results: In group 1 (asymptomatic patients) 10 occult malignancies were detected due to the additional ultrasound examination, i.e. one diagnosed malignancy in 70 examined patients (detection rate 1.4%). By reason of false positive ultrasound results, 65 additional control-ultrasounds, 14 additional MRI examinations and finally 22 biopsies of benign lesions were unnecessarily conducted. Weighing in the total costs for ultrasound, MRI and biopsy, an amount of 4150€ (5290$) was spent to find one additional cancer.In group 2, apart from the symptomatic lesions, 3 occult malignancies were exclusively identified due to the ultrasound examination (detection rate 1.7%). On the other hand, false positive ultrasound results caused 7 additional control-ultrasounds, 14 additional MRIs and 11 biopsies of benign lesions. Hence, an amount of 4410€ (5620$) was spent to identify one additional malignancy by the means of additional ultrasound in this group.Overall, 50 patients (5.7%) received biopsy due to false positive results either in ultrasound or mammography, but these patients claimed on questioning not to feel “troubled and anxious”, but “saver and more carefully looked after”.Discussion: Regarding our results, we strongly recommend the routine use of ultrasound in breast cancer follow-up for both, asymptomatic and symptomatic, women, as occult malignancies can be identified cost-efficiently, although additional ultrasound may also result in higher false positive findings.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5027.
A Prospective Study of Computerized Digital Infrared Image Analysis (NoTouch BreastScanTM) in Biopsy Proven Breast Cancers.
Authors: Nair N. , Thakur M. , Hawaldar R. , Nadkarni M. , Parmar V. , Badwe R. 
Published: December 2010

Abstract
Introduction: Early detection of breast cancer is known to have a more favourable outcome. Currently clinical breast examination and imaging modalities, primarily mammography are used for screening purposes. In India, more than 85% of the population is below the age of 50 years, wherein the sensitivity of mammography is at best 64%. Additional drawbacks of the procedure are physical discomfort and ionizing radiation dose to the patient. So newer techniques have been investigated which detect cancer induced neovascularity with digital thermal imaging. The purpose of this clinical study was to determine the efficacy of a software assisted thermal image analysis tool to distinguish between benign and malignant lesions of the breast.Methods: A prospective study was conducted in women who presented to the breast clinic with clinically or mammographically suspicious breast lesions. They also underwent thermal imaging of the breast. All mammographically suspicious lumps were subjected to histopathological confirmation. The mammography and infrared (IR) reports were compared to the histopathology.Results: In 90 women, 180 breasts were independently analyzed by both digital IR software analysis and mammography. Eighty five out of these 180 had suspicious lesions on mammography or clinical examination which were subjected to pathological confirmation. Mammography being the present diagnostic gold standard, all normal mammograms in clinically normal breast were considered as non-malignant. The sensitivity and specificity of digital thermography in detecting malignant lesions was 88.24% and 70.52% respectively with NPV of 87.01% and PPV of 72.82%. While for mammography the sensitivity and specificity were 96.25% and 96.7% with NPV of 96.7% and PPV of 96.25%. In women below 50 years of age (62/90) the sensitivity and specificity of digital thermography was 89.83% and 64.61% with NPV of 87.5% and PPV of 69.74%. Further, in the same subset no statistically significant difference was detected in the sensitivity of digital thermography to that of mammography (p = 0.7263).Conclusion: Our initial experience shows that the detection rate by digital thermal imaging is comparable to mammography in clinically palpable breast tumors. We also note that there is no significant difference in sensitivity of thermal imaging in women on either side of 50 making it a potentially testable tool for screening in younger women.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5028.
Isolation of Tumor Initiating Cells with Metastatic Potential from Human Primary Invasive Ductal Carcinoma.
Authors: Marsden C. , Marsden C. , Wright M. , Wright M. , Carrier L. , Carrier L. , Pochampally R. , Pochampally R. , Pochampally R. , Rowan B. , Rowan B. 
Published: December 2010

Abstract
Disseminated breast cancer cells may be present at distant sites at the time of primary diagnosis of breast cancer in patients that exhibit no outward signs of clinical metastasis. It is hypothesized that early breast cancer metastasis is initiated by a small population of breast tumor initiating cells (bTICs) within the primary tumor that are inherently resistant to chemotherapy and hormonal therapy. To better understand the biological pathways that permit bTICs to metastasize and to evade current breast cancer therapies, bTICs have been isolated from breast cancer biopsies from patients diagnosed with primary invasive ductal carcinoma. Breast cancer needle biopsies from primary tumors were obtained during the routine care of patients with consent and IRB approval. Core biopsies were mechanically and enzymatically dissociated, yielding a single cell suspension which was subsequently cultured under non-adherent and serum-free conditions to obtain tumorspheres. Injection of about 500 bTICs into the mammary fat pad of female nude mice resulted in tumor formation at the site of injection within two months that was maintained as a small palpable mass for at least six months. H+E staining of sections of the primary tumors revealed complex cellular organization and both microvascular and macrovascular structures. Serial transplantation of the primary tumors from the 6/7 samples resulted in tumor formation at the site of injection. Upon primary tumor formation in the mammary fat pad, metastatic human breast cancer cells were detected within the lungs, liver, brain and bone marrow (femur) from 5/7 tumors after six months. Metastatic cells were detected by PCR for an alpha-satellite sequence in the centromeric region in human Chromosome 17, and by in situ hybridization using an human specific Alu DNA oligonucleotide probe. Metastatic bTICs were mostly detected as single cells or small clustering of cells present throughout the metastatic organ. These data demonstrate that cells with the phenotype of “tumor initiating cells” can be isolated from primary biopsies of human invasive ductal carcinoma and cultured in vitro. Unlike direct heterotransplant tissues from primary tumor biopsies, the majority of bTICs samples form tumors when injected into immunodeficient mice and further exhibit a highly metastatic phenotype.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 504.
Identifying Symptom Clusters in Breast Cancer: Implications on Patient Quality of Life.
Authors: Lis C. , Birdsall T. , Stark J. , Cain L. , Campbell K. , Gilbert K. , Gupta D. 
Published: December 2010

Abstract
Background: Patients undergoing treatment for advanced cancer often experience multiple symptoms. These symptoms occur with varying frequency, intensity, and impact. Pain, fatigue, insomnia, anorexia and dyspnea are consistently among the 10 most prevalent symptoms associated with cancer and its treatment. We conducted a multivariate analysis to investigate the impact of cancer symptoms on patient quality of life (QoL) in breast cancer.Material and Methods: A consecutive series of 226 breast cancer patients treated at the Cancer Treatment Centers of America at Southwestern Regional Medical Center between Jan 2001 and Nov 2006. Cancer symptoms were assessed using the symptom subscales of European Organization for Research Treatment of Cancer - Quality of Life Questionnaire (QLQ-C30). Symptom scores range from 0-100 with lower scores indicating better while higher scores indicating worse symptoms. QoL was assessed using Ferrans and Powers Quality of Life Index (QLI). QLI measures overall QoL and QoL in 4 major subscales: health/physical, social/economic, psychological/spiritual, and family. QLI scores range from 0-30 with higher scores indicating better QoL. The relationship between QLQ-C30 symptoms and QLI was evaluated using multivariate linear regression.Results: Of 226 patients, 98 were newly diagnosed while 128 had failed prior treatment before coming to our hospital. The mean age was 52.5 years (range = 27-82 years). We found that every 10 unit increase in fatigue (p=.004) and pain (p=.001) was significantly associated with 0.65 and 0.66 unit decline in QLI health/physical subscale after controlling for age, treatment history, stage at diagnosis and other cancer symptoms. Similarly, every 10 unit increase in insomnia (p=.02) was significantly associated with 0.35 unit decline in QLI family subscale. Finally, every 10 unit increase in pain (p=.01) and insomnia (p=.03) was significantly associated with 0.34 and 0.21 unit decline in overall QoL.Discussion: We found fatigue, pain and insomnia to be independent predictors of QoL after controlling for each other, age, treatment history and stage at diagnosis. Recognition and timely treatment of symptom clusters could result in improved QoL in patients with breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5043.
Medical Ozone (O3) Oil or Gas Applications Heal Osteonecrosis of the Jaw (ONJ) in Patients Treated with Bisphosphonates (BPs). Preliminary Results of a Single Arm Study.
Authors: Ripamonti C. , Maniezzo M. , Ghiringhelli R. , Cislaghi E. , Mariani L. 
Published: December 2010

Abstract
Treatment of bone metastasis with BP is aimed at preventing skeletal related events (SREs) and rarely leads to ONJ (&lt;1%) (Hoff, JBMR. 2008). Preventive dental care is a simple and effective way to reduce the risk reduction of ONJ in 75% of the cases (Ripamonti, Ann Oncol. 2009). To date, there are still no standardized therapy for the treatment of ONJ. We report the effect of localized of O3 oil or gas application in cancer patients (12 breast cancer, 4 prostate cancer, 2 lung cancer, 1 NHL, 3 multiple myeloma) with ONJ observed in our institution. Patients had previously received nitrogene-BPs treatment in the absence of odontoiatric preventive measures. All the patients were in had stable disease without progression; 10 of them had ONJ lesions ≤ to 2.5 cm.O3 oil suspension applications on ONJ lesions ≤ 2.5 cm was carried out with localized applications directly on the lesions; patients with larger lesions (≥ 2.5 cm) were treated with the ozone gas locally applied. All the patients received treatment of O3 oil every third day and all of them were treated with antibiotic therapy (azithromycin, 500 mg/day) 10 days prior the initiation of the treatment with O3 oil. The statistical analysis is based on a Simon two-stage design, the second stage is on-going. In this preliminary analysis we focus on 10 patients treated with O3 oil with a medium follow up of 8 months, and 12 patients on medical gas ozone.73% of the patients (n=16) showed complete response in terms of radiological lesion disappearance with complete reconstruction of oral tissue. Among them, fourteen patients developed spontaneous sequestrum with expulsion of the necrotic bone whereas in 2 patients with large extension of bone involvement surgical intervention was necessary.Seventy percent of the patients treated with O3 oil experienced a complete response after 4 applications whereas patients treated with gas needed 4 to 16 applications (depending on the severity of the lesion). No patients presented adverse events related to the use of ozone treatments. Six patients are still on treatment and are improving as well.According to these results few application of O3 oil suspension in patients with smaller lesions and gas medical ozone for wider lesions following antibiotic therapy can rapidly lead to complete healing of ONJ. Further cases and complete follow-up data are required. These data indicate that ONJ is a manageable condition which can be not only prevented by means previously dental examination but also healed with medical ozone applications.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5046.
Pharmacological Inhibition of Signaling through the Activin Receptor Type IIa Prevents Primary Tumor Growth and Skeletal Metastases in Mouse Models of Breast Cancer.
Authors: Mulivor A. , Barbosa D. , Kumar R. , Underwood K. , Ucran J. , Seehra J. , Pearsall R. 
Published: December 2010

Abstract
Breast cancer cells have a strong propensity to metastasize to bone, resulting in debilitating complications such as intractable bone pain, spinal compression, pathological fractures, or loss of mobility and function. Anti-resorptive agents, such as bisphosphonates, are commonly used to halt the loss of bone, but do not stimulate the formation of new bone. Previous data demonstrated that treatment with an activin antagonist, a soluble form of the extracellular domain of the activin receptor type IIA (ActRIIA) fused to a murine IgG-Fc fragment (RAP-011), can restore bone mass in ovariectomized mice with established bone loss and prevent bone loss in a murine model of multiple myeloma.The goal of the current studies was to establish the ability of RAP-011 to directly inhibit breast cancer cell proliferation, delay primary tumor growth and prevent skeletal metastases. Bioluminescent breast cancer cells (MCF-7-luc and MDA-MB-231-luc-D3H2LN) were administered orthotopically to establish a primary tumor model or by intracardiac injection to establish a metastatic breast cancer model. Both studies were performed using athymic nude mice that had been pretreated for 2 weeks with RAP-011 (10 mg/kg S.C. twice weekly) or vehicle (VEH).In vitro studies demonstrated that activin A stimulated proliferation of some tumor cell lines, while the addition of soluble ActRIIa blocked the stimulation. In the orthotopic models of breast cancer RAP-011 treated mice had significantly smaller primary tumors as early as 3 weeks post-inoculation. RAP-011 treated mice had tumors that remained significantly smaller for the duration of the 10 week study (-60%, p&lt;0.02).In the model of metastatic breast cancer, RAP-011 treated mice displayed lower levels of hind limb, mandible and lung metastases compared to VEH-treated mice. RAP-011 treated mice had reduced tumor burden (-70%, p&lt;0.001), fewer osteolytic lesions (-45%, p&lt;0.05) and increased overall survival by 11 days compared to VEH-treated mice. DXA scanning of the mice revealed RAP-011 treated mice had a significant increase in bone mineral density compared to the VEH treated mice (+10%, p&lt;0.05), reflecting the decreased levels of osteolytic metastases. Histological analysis of the femur and tibia confirmed increased levels of tumor growth and osteolytic lesions, as well as decreased levels of trabecular bone volume in VEH treated mice.These data support the role of Activin in the establishment and growth of tumors and that the use of a soluble ActRIIA receptor can prevent primary tumor growth and inhibit metastases in patients with breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5058.