bluuebunny/crossref_metadata_2025_split huggingface dataset:
PE-PCR, a novel method for detection of mutations in blood-cell-free DNA.
Authors: Platica Ovidiu , Khazan Mikhail , Martinez Manuel 
Published: March 2020

e12016 Background: During the past few years, the “personalized” therapy based on specific tumor molecular alterations has become the standard of care of cancer patients . Recently, it has been shown that blood DNA is released from normal as well as tumor cells as a high molecular weight nucleic acid and carries the same genetic abnormalities as the cells of origin. However, the identification of these DNA alterations is difficult since the blood tumor DNA is found in very low concentration and it is mixed with a huge amount of normal homologous DNA. Therefore, most methods able to detect such abnormalities in cells are not applicable for blood cell free DNA. We report here a simple novel technology for mutation detection in blood DNA. Methods: The serum DNA is subject to two PCR rounds; in the first round, only DNA fragments containing the mutation are amplified by an extension primer encoding the mutation at its 3’ terminus. The DNA is then re-amplified by nested PCR for 40 cycles and the extension of mutated primer is detected by gel electrophoresis. The method was tested with DNA from the human lung cancer cell line A549 (ATCC # CCL-185) and was found to detect mutations in the presence of 10 12 [OP1] fold excess of normal DNA. Results: The sera from 10 patients with localized and metastatic lung (6) and pancreatic carcinomas (4) were tested for the presence of mutations in Kras and P53 genes. Seven patients had a mutation in a least one gene. Eleven patients without any clinical evidence of cancer tested negative. Conclusions: PE-PCR is a simple sensitive method for mutation detection in blood cell-free DNA, requiring only one ml blood and less than a 48 hour work. This method can potentially be used for mutation detection in most of the genes of clinical interest, as a non-invasive research tool, for early detection of tumor recurrence and possibly for early diagnosis of cancer when surgery can be curative.
Relationship between cancer and allergy.
Authors: Carneiro Bruno Gustavo Muzzi Carvalho , Petroianu Andy , Carvalho Rafael Augusto Ribeiro , Ribeiro Thiago Neto , Rodrigues Ana Maria Santos 
Published: March 2020

e12018 Background: Many studies have suggested an inverse association between allergies and cancer, while others have found no relation between them, and still others have shown an increased risk of cancer in allergy patients. The conflicting findings from prior studies are partially due to the chosen research method, such as different definitions and measures for atopy, in addition to variations in the control of confusion factors, such as smoking and obesity. Objectives: Verify if there is a relation between certain types of cancer and allergies; investigate if there is a difference between individuals with and without cancer in relation to allergies. Methods: Case-control study carried out at the Alberto Cavalcanti Hospital of the Hospital Foundation of the State of Minas Gerais (FHEMIG), Brazil, from 2009 to 2011. The study included patients over 18 years of age, from both genders, who presented a diagnosis of cancer, as compared to healthy individuals, paired by gender and age. An anamnesis was gathered considering the medical history of the allergy, as diagnosed by a doctor, as well as the patients’ habits, associated illnesses, and the use of medications. For cancer patients, data concerning the tumor were recorded. Subsequently, an allergy percutaneous test was performed in each group to detect allergic hyperreactivity toward common inhalable, bacterial, and food antigens within our everyday environment. A blood sample was collected to quantitatively evaluate the eosinophils. Results: Both groups were paired according to interest variables, and eventual deviations were adjusted by means of multivariate analysis. Reports of allergies occurred in 30% of the patients in the cancer group, as compared to 53% in the control group (p<0.05), whereas in the cutaneous tests, a greater positivity occurred in the cancer group (69%) than in the control group (51%, p<0.05). No difference in the eosinophil values could be observed within the groups. Conclusions: Cancer patients present fewer allergies. By contrast, in cancer patients, positive cutaneous tests detected allergies which did not correspond to the clinical findings. Therefore, in cancer patients, the positive cutaneous test for allergies does not present a direct relation to the presence of clinically detectable allergies.
Disease-free survival pattern in breast cancer patients in India treated in a single institution.
Authors: Ajaikumar Basavalinga S. , Gopinath Kodaganur Srinivasachar , Srinath B S , S Ramesh Bilimagga , Rao Nalini K , Patil Shekhar , Diwakar Ravi B , Prabhudesai Shilpa A. , Kallur Kumar G , Raghavendra Rao M. , Shashidhar H P 
Published: March 2020

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.
Analysis of clinical features of ovarian cancer (OC) and breast cancer (BC) among BRCA-mutated (BRCA+) and sporadic (NH) double tumors.
Authors: Nicoletto Maria Ornella , Borgato Lucia , Artioli Grazia , Perin Alessandra , Zustovich Fable , Ghiotto Cristina , Koussis Haralabos , Cappetta Alessandro , Mocellin Simone , Furini Lara , Dalla Palma Maurizia , Ercoli Alfredo , Litta Pietro , Nardelli Giovanni B. , Zagonel Vittorina 
Published: March 2020

e12037 Background: Women BRCA+ are at significant risk of developing both OC and BC. Double tumors could arise also in NH patients. Whether the clinical outcome of double OC and BC is different in BRCA+ and in NH subjects is unknown. Methods: The databases of the Istituto Oncologico Veneto (IOV), Medical Oncology Department of Mirano (VE) and Thiene (VI) were searched to identify the clinical and pathological features of (BC) and (OC) arisen in BRCA+ subjects as well as patients with both malignancy but tested negative/no-tested/unknown for BRCA1/2 mutation (NH). The primary endpoint was to establish if OC instead of BC needs a more intensive follow-up because it principally affects patient’s prognosis. Patients were censored at last follow-up or death (any cause) for determination of overall survival (OS). OS estimates were determined using the Kaplan-Meier method and compared by means of log-rank test. The Fisher’s exact test and the t-test were used to compare frequencies and means between groups, respectively. Results: 24/31 (77%) BRCA+ and 30/49 (61%) NH had BC as their first malignancy (p=0.15). Among NH, 20 were BRCA test negative, 20 were untested and 9 unknown. BRCA+ were younger than NH at diagnosis of first malignancy (mean age 51 vs 56y, p=0.055). Bilateral BC was more frequent in BRCA+ than in NH (78.6% vs 28.6% p=0.001). Stage III-IV OC at diagnosis were 74% in BRCA vs 61% in NH (p=0.34). Locally advanced (stage II-III) BC was significantly more frequent in BRCA+ vs NH (75% vs 42%, p=0.03). No OS difference was observed between BRCA+ and NH subjects (P=0.99). Death for progression of ovarian cancer was observed in 11/31 (35%) in BRCA+ vs 10/49 (20%) patients in NH (p=0.19). No progression of breast cancer was reported in either groups. Conclusions: OC is the killer malignancy among patients affected by OC and BC, both in BRCA+ and in NH subjects. In patients with double tumors, irrespective of their pathological features, a more conserving management for BC and an intensive follow-up for OC are suggested.
Effect of interferon-α/β on temozolomide activity against MGMT-positive glioma stem-like cells in vitro and in vivo.
Authors: Chen Zhong-ping , Shen Dong , Wang Jie , Yang Qun-ying 
Published: March 2020

e12503 Background: O6-methylguanine DNA methyltranferase (MGMT) is one of the main mechanisms of chemoresistance for alkylating agents in malignant gliomas. Recent studies have showed that glioma stem-like cells (GSCs) could be the main reason for tumor recurrence and chemoresistance. In this study, we aimed to explore the effects of interferon-α/β against MGMT-positive glioma stem-like cells, and to investigate whether interferon-α/β can enhance the efficiency of temozolomide (TMZ) and the possible mechanism Methods: The growth inhibition effect of TMZ, with interferon-α or interferon-β, against the MGMT-positive GSCs from human glioma cell lines U251 and SKMG-4 (U251G and SKMG-4G) was evaluated by using Cell Counting Kit-8 (CCK-8) assay in vitro, and in xenograft models. MGMT and NF-κB expression in the tumor samples were determined by RT-PCR and Western blot analysis. Results: Our results revealed that the anti-tumor activity of TMZ was significantly enhanced by combined using interferon-α/β in vitro. In xenograft models, the tumor growth inhibit rate (IR) of TMZ to SKMG-4G and U251G was 35.2%±2.28% and 16.7%±1.96%, respectively. When TMZ combined with interferon-α or interferon-β, the IR to SKMG-4G was 58.4%±4.34% and 63.4%±1.08%; and to U251G was 41.1%±8.66% and 44.5%±1.90%, respectively(P<0.05). The expression of NF-κB and MGMT in MGMT-positive GSCs decreased significantly in both mRNA and protein levels after using interferon-α/β. Conclusions: Our results indicate that IFN-α/β can enhance the sensitivity of TMZ, possibly through down-regulate NF-κB expression resulting in lower MGMT transcription expression.
Prognostic factors in survival of patients with cerebral metastases.
Authors: Markulin-Grgic Lijerka , Kukura Vlastimir 
Published: March 2020

e12505 Background: The problem of cerebral metastases is a great one and seems to become more and more important thanks to earlier diagnosis and the possibilities of effective treatment. In this analysis 330 patients with cerebral metastases, treated at the Clinic of Oncology, School of Medicine, Zagreb, Croatia, over 13 years, from 1995 - 2007 are dealt with. The most common primary tumor was bronchus carcinoma in 201/330 patients (60.91%), then breast carcinoma in 48/330 patients (14.54%), melanoma in 16/330 patients (4.85%), gastrointestinal tumors in 17/330 patients (5.15%), hypernephroma in 9/330 patients (2.73%), ovarian carcinoma in 10/330 patients (3.03%), cervical small cell carcinoma in 4/330 patients (1.21%), testicular tumors in 5/330 patients (1.52%) and in 20/330 patients (6.06%) the primary was not found. Methods: The patients were treated by surgery, radiotherapy and chemotherapy in various combinations. Results: There is a significantly better survival in female patients with cerebral metastases from breast carcinoma in comparison to other primary tumors (p<0.001). The patients with longer symptom-free period up to the diagnosis of the secondaries in the brain had significantly better survival (p<0.001). Better survival was achieved in younger patients (p<0.05). Conclusions: Considering the applied therapy methods, the best survival results were obtained in patients treated by a combination of surgery, radiotherapy and chemotherapy.
“Long extended” temozolomide in a selected population with not radically resected high-grade gliomas.
Authors: Spinelli Gian Paolo , Lo Russo Giuseppe , Miele Evelina , Alberti Antonio Maria , Strudel Martina , Stati Valeria , Zoratto Federica , Papa Anselmo , Rossi Luigi , Verrico Monica , Basso Enrico , Giordani Erika , Zaccarelli Eleonora , Minozzi Marina , Codacci Pisanelli Giovanni , Tomao Silverio 
Published: March 2020

e12510 Background: Despite the important progress in the treatment of solid tumors, high grade gliomas (HGGs) remain neoplasm with poor prognosis, especially when are not radically resected. Here we report the results of a selected population treated with standard schedule of Radiotherapy (RT) + Temozolomide (TMZ) followed by TMZ until progression. Methods: From January 2008 to January 2010, 14 newly diagnosed HGG patients, with median age of 50.6 years (range 27-75 yrs), were enrolled at Oncology Unit of S. Maria Goretti Hospital in Latina (University of Rome “Sapienza”). All patients were not radically resected and with ECOG PS=O. Furthermore patients were selected according to O6 Methyl-Guanine-DNA-Methyl Transferase (MGMT) promoter methylation status. Only methylated patients were included in our study. After surgery, patients received standard treatment with TMZ (75 mg/m2) concomitant with RT (60 Gy total dose). After a break of six weeks, Magnetic Resonance Imaging (MRI) was performed and all patients with stable or responsive disease received TMZ (150mg/200mg/m2/d x 5dq 28d) until progression. The response to treatment was evaluated according to RANO criteria Results: In our study the results showed one year overall survival (OS) and progression free survival (PFS) rates of 85,7% and 71,4% respectively. Moreover we observed two years OS rate of 70% and two years PFS rate of 10%. A total of 108 cycles of adjuvant TMZ were administered with average number of 9 per patient (range 1-16). The most frequent side effects observed were haematological toxicity and fatigue. Thrombocytopenia (G2-G3) was observed in 42% of patients, neutropenia (G2-G3), fatigue (G2-G3) and nausea (G2-G3) in 30%, 32% and 25% of patients respectively. Conclusions: Despite the small number of patients, our experience suggests a manageable safety profile and a good efficacy of TMZ until progression in a selected population of patients (HGGs not radically resected, with a good ECOG PS). These data also confirms the literature knowledge, underlining the prognostic positive impact of MGMT promoter methylation in patients with HGG.
Phase Ib study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A) in combination with bevacizumab (bev) with or without paclitaxel.
Authors: Goldman Jonathan Wade , Gordon Michael S. , Munster Pamela N. , Bergsland Emily K. , Moore Amy Patricia , Bai Shuang , Hegde Priti , Fredrickson Jill O. , Chang Ilsung , Chandler G. Scott , Funke Roel Peter , Rhee Ina Park , Chen Daniel S. , Rosen Lee S. 
Published: March 2020

e13000 Background: Epidermal growth factor-like domain 7 (EGFL7), is a vascular-restricted, tumor selective, extracellular matrix protein that forms peri-vascular tracks and promotes endothelial cell adhesion and survival. These activities are inhibited by the huMAb anti-EGFL7 (MEGF0444A), which significantly enhances the efficacy of anti-VEGF in murine tumor models. A Phase Ia dose escalation of single agent MEGF0444A demonstrated no dose-limiting toxicities (DLTs). Methods: A standard 3+3 dose escalation design was used to study safety, PK, PD, and anti-tumor activity of MEGF0444A in a 2-arm Phase Ib trial in patients (pts) with advanced solid tumors. In Arm A, 22 pts received MEGF0444A at doses of 2, 5, or 10 mg/kg with bev 10 mg/kg q2w. In Arm B, 18 pts additionally received paclitaxel 90 mg/m2 weekly. Subsequent Arm A expansion cohorts have examined flat dosing of MEGF0444A (600 mg) as a rapid infusion, serial tumor biopsies, and pts with renal cell carcinoma (RCC), respectively. Circulating progenitor cells (CPCs) and dynamic contrast enhanced MRI (DCE-MRI) were assessed as PD biomarkers. Results: The combination of MEGF0444A and bev with or without paclitaxel was well-tolerated without DLTs, exacerbation of bev-related adverse events (AEs), or AEs attributed to rapid infusion. MEGF0444A demonstrated linear PK, and flat dosing yielded MEGF0444A exposures similar to those predicted using Phase Ia weight-based dosing data. CPCs decreased in a subset of pts at the 5 mg/kg q2w dose. DCE-MRI showed a trend toward decreased Ktrans at this dose, supporting combination activity with bev. Eight partial responses, 2 in Arm A and 6 in Arm B, were observed across multiple tumor types. Conclusions: MEGF0444A has demonstrated safety, favorable PK, and clinical activity in combination with bev and bev/paclitaxel. PD biomarker modulation supports a recommended Phase II dose equivalent to 5 mg/kg q2w. RCC and tumor biopsy cohorts remain active. Randomized Phase II trials of MEGF0444A in combination with chemotherapy and bev in colorectal cancer and non-small cell lung cancer are underway.
Bronchial artery infusion of recombinant adenovirus-p53 and chemotherapeutic agents in treatment of bronchogenic carcinoma in advanced stage and failed to response to standard treatments.
Authors: Zu Maoheng , Zang Qingqiao , Wei Ning , Xu Wei Xu 
Published: March 2020

e13004 Background: Patients with advanced bronchogenic carcinoma (BC), who failed common standard treatments, poses a big challenge for clinicians. Here we report success cases of using bronchial artery infusion of recombinant adenovirus-p53 (rAd-p53) and chemotherapeutic agents in treatment of advanced BC failed to response to standard treatments. Methods: Sixteen patients with advanced unresectable BC, who failed standard chemo- and radio-therapy, were included in this study. There were 11 males and 5 Females with an average age of 59.4 years old. They received bronchial artery infusion of 2×1012 rAd-p53 viral particles (VP), 40 mg of cisplatin (PPD), 20 mg of pirarubicin (THP), 0.5 g of 5-Fu, and 30 mg of endostatin. The infusion was given daily for 3 days. Response rate and overall survival were evaluated. Results: At 3 months follow-up after the last infusion, the partial response rate was 68.8% (11/16). Symptoms like cough and short of breath were significantly relieved in those patients responding to the treatment. Overall survival rate of one year was 81.3% and median survival time was 11.6 months. No significant adverse events were found in those patients. Conclusions: Bronchial artery infusion of rAd-p53 combined with chemotherapeutic agents is effective and safe treatment for patients with advanced BC, who failed common standard treatments.
Breast cancer stem cells: A novel therapy for breast cancer.
Authors: Mukhopadhyay Soma , Gangopadhyay Sudeshna , Dasgupta Swati , Sengupta Saubhik , Ray Ujjal Kanti , Hor Pooja , Mukhopadhyay Ashis 
Published: March 2020

e13030 Background: Simple BRCA screening is insufficient for ‘event-free survival’ as breast cancer is clinically and pathologically an extremely heterogeneous disease. Targeting Breast Cancer Stem Cells (BCSCs) present in bone marrow and breast tissues is a lucrative alternative. Identification of BCSCs is salient aspect of our research. Invasive and mesenchymal property of BCSCs with CD44+/CD24low/ALDH1+ phenotype has made them a promising target for eliminating metastatic capacity of primary tumors. We hypothesize that ability to therapeutically attack stem cell hinges upon identifying unique targets like cell surface markers and this will decide development of specific target therapies. Methods: A total of 10 early chemo-naive patients with biopsy proven triple-negative metastatic breast cancer in the age group of 18-36 yr.s (mean age 28 yr.s) were selected randomly and tested for CD44/CD24 cell surface markers following immunosorting using magnetic cell sorter and immunophenotyping by flowcytometric analysis. Isolated BCSCs were cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel. Correlation was drawn between cell differentiation, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. % of BCSCs in pre- and post-chemotherapeutic condition was further compared. Results: We have detected BCSCs in 90% of cases. Among positive samples, 89% patients showed platinum sensitivity and rest were found to be anthracycline sensitive. No sensitivity to docetaxel was observed. In lieu of this, cisplatin was applied in vivo and % of BCSCs came down to 6.58% from initial 11.16% (for a representative case). Conclusions: Thus primary aim to target BCSCs at the onset of tumors in breast cancer patients to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival. Finally, if no BCSCs prevail after chemotherapy, then patients would be kept under observation and if traces are found, we would proceed to targeted therapy trial like PARP inhibitor or autologous stem cell replacement.
Fractures and health care resource use in cancer patients with chemotherapy-associated peripheral neuropathy (CAPN).
Authors: Ganguli Arijit , Reilly Patrick J , Ray Saurabh 
Published: March 2020

e13038 Background: Chemotherapy has been associated with increased risk of fractures1. This study examines the real-world incidence of fractures and healthcare resource use (HRU) that may be associated with CAPN in cancer patients. Methods: A retrospective analysis utilized a national health insurer claims -database (2001-2009), to identify patients ≥18 yrs with a cancer ICD-9-code (140-239) and a chemotherapy drug code (J9xxx). The 1st chemotherapy date was the "index date." Patients with a record of peripheral neuropathy (PN) in the pre-index date were excluded. Patients with a PN post-index were matched with no-PN post-index (non-PN) based on gender, age and index date. Both groups were compared for number of fractures, HRU (hospital outpatient (OP), office, and emergency-room [ER] visits) and all-cause costs in their 365-days post-index period. Time to 1st fracture post-index was compared using Kaplan Meier time to event analysis. Results: Of 34,625 patient meeting the inclusion criteria, 1675 patients (4.3%) formed the PN group and were matched to non-PN group. At baseline, mean age was 54.9 yrs, 62.5% were females, and no difference in % of bone metastasis (p=0.12) between the groups. In PN group, 5.3% (n=87) had a fracture 365-days post-index compared to 3.5% (n=58) in non-PN group (p<0.05). Mean days to fracture from index date in PN group was shorter than the non-PN group (150.9 vs. 153.4, p<0.05). In PN group, annual mean number of OP visit (14.6 vs. 12.0, p<0.0001), ER visit (0.47 vs. 0.30, p<0.001), and office visits (30.4 vs. 23.3, p<0.0001), were higher compared to non-PN group. Annual healthcare cost of PN patients was 21% higher than non-PN patients ($64,578 vs. $53,221) and CAPN-related cost in PN group was estimated to be $5,580 annually. Conclusions: Patients with CAPN were associated with higher incidence of fractures, HRU and cost.