bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bin1 expression is lost in breast cancer
Authors: Ghaneie A. , Duhadaway J. B. , Zemba-Palko V. , Prendergast G. C. 
Published: March 2020

10772 Background: Immune evasion is a major factor that limits the success of current treatment strategies with cytotoxic agents and immune therapy for breast cancer. Elevation of the immunomodulatory enzyme IDO in tumor cells was recognized as a mechanism of immune escape. Studies show that IDO is under genetic control of Bin1. Bin1 is a MYC-interacting adaptor protein which is attenuated in many malignancies and mouse knockout studies indicate that Bin1 loss elevates the STAT1- and NF-kB-dependent expression of IDO, driving escape of oncogenically transformed cells from T cell-dependent antitumor immunity. Mouse studies show that small-molecule inhibitors of IDO cooperate with cytotoxic agents to elicit regression of therapy refractory tumors. These findings suggest that Bin1 loss promotes immune escape by deregulating IDO and that IDO inhibitors may improve response to cancer chemotherapy. Methods: A cohort of breast cancer specimens collected at our institution over a five-year period was used for this retrospective study. The cohort consists of 56 specimens of early stage and 37 specimens of advanced stage ductal adenocarcinomas of the breast. Using immunohistochemistry, specimens were examined for the loss of BIN1 expression. Results: Bin 1 was lost in a significant fraction of breast cancer specimens. In the early stage group 76% had loss of nuclear expression and 23% loss of cytoplasmic expression. In the advanced stage group 84% had loss of nuclear staining and 38% had loss of cytoplasmic staining. Conclusions: Bin1 was lost in a significant fraction of breast cancer specimens. This finding indicates that loss of Bin 1 may play a significant role in immune evasion in human breast cancer. Animal studies have shown that loss of Bin1 can be antagonized by IDO inhibitors. This could have a significant implication for the treatment of human breast cancer. Immune escape induced by Bin1 loss could be restored through the administration of immunomodulators such as 1MT (1-methyltryptophan) in combination with chemotherapy. This could lead to a novel approach in the treatment of breast cancer. No significant financial relationships to disclose.
Detection of doxorubicin cardiotoxicity in patients with breast cancer by 99mTc-MIBI myocardial perfusion tomography
Authors: Morales-Vasquez F. , García S. , Lopez-Basave H. , Altamirano-Ley R. 
Published: March 2020

10775 Background: Cardiotoxicity is a well-known side effect of several cytotoxic drugs especially of the anthracyclines and can lead to long term morbidity. Endomyocardial biopsy is the only specific test for early diagnosis of anthracycline-induce toxicity. Efforts are continuing on finding a more sensitive and reliable predictor of eventual clinic cardiac dysfunction. Therefore, it is crucial that careful monitoring to identify those patients patients who are at risk of developing unpredectible and some times-irreversible dysfunction. Serial measurement of left ventricular ejection fraction by radionuclide angiography remains a useful and widely adopted modality in monitoring patients that are receiving doxorubicin. Objective: To investigate the value of 99mTc-MIBI myocardial perfusion tomography to detect myocardial damage in patients with breast cancer under chemotherapy. Methods: Thirty patients were examined from May to December 2000 by electrocardiogram (ECG), nuclear angiography for detecting left ventricular ejection fraction (LVEF) and 99mTc-MIBI myocardial perfusion was performed before chemotherapy and after chemotherapy. Results: Fifteen patients were treated by continuos infusion over 24 hr, nine patients over 48 hr and 6 patients were treated by bolus. The patients presented with a decrease of > or = 9% in absolute ejection fraction at 200–320 mg/m2 with 99mTc-MIBI and 5% with nuclear angiography. Gated myocardial perfusion scintigraphy results were abnormal in four patients (12.9%). All patients were treated by continuos infusion and the radiotherapy was absent. Other factors were investigated: hypertension, diabetes, smoker and obesity. Conclusions: 99 mTc-MIBI studies are helpful in the assessment of doxorubicin cardiotocixity. Anthracyclines induced myocite injury symptomatic or asymptomatic; uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates. The 99-mTc-MI BI imaging may be a sensitive method for non invasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease. Doxorubicin cause silent myocardial ischemia. No significant financial relationships to disclose.
Multicenter, prospective study of radiotherapy without surgery after AC followed by weekly paclitaxel for patients with inflammatory breast cancer: SBCCSG-04 study
Authors: Tabei T. , Sato K. , Inoue K. , Nakano S. , Kai T. , Futsuhara K. , Yamashita S. , Saito T. , Kuroda T. , Suemasu K. 
Published: March 2020

10783 Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease with a dismal outcome. It is still an open debate whether surgery is beneficial for patients with IBC. This study was conducted to evaluate treatment results when patients were treated by chemotherapy and radiotherapy (CRT) alone. Methods: 52 pts with nonmetastatic IBC were enrolled for a prospective registration trial from 9/01–11/04. A diagnosis required the presence of erythema, ridging, or peau d’orange, with or without dermal lymphatic invasion (DLI). All patients were invited to participate for an experimental protocol; 4 cycles of AC and 12 cycles of weekly paclitaxel (80 mg/m2) followed by radiotherapy. In patients who did not agree to the protocol, the decision about treatment was left to the patients/investigators. The primary endpoint was distant-disease-free survival, and the further endpoints were locoregional relapse (LR) and overall survival. Results: The mean follow-up was 25.7 months. 24 pts (46.2%) were planned for the protocol, but one pt (4%) was receipt surgery. Otherwise, 18 (64%) out of 28 pts have accepted mastectomy. The 2-year distant-disease-free, LR, and overall survival in patients treated with and without the protocol was 35.2 vs 61.0% (HR = 2.4, 1.1–5.3) and 55.2 vs 83.6% (HR = 2.9, 1.1–7.8), respectively. Surgery was not associated with the risk of LR (p = 0.48). There was marginally worse prognosis in patients with DLI. Conclusions: There was a limitation because this comparison had not been conducted a randomized fashion. However, CRT alone would be a feasible treatment schedule for a moderate percentage of patients with IBC. No significant financial relationships to disclose.
Experimental study on Chinese ink as the dye for the sentinel lymph node biopsy
Authors: Wang S. , Xu K. , Liu X. , Zhou Q. , Geng Q. , Geng Q. 
Published: March 2020

10785 Background: Sentinel lymph node biopsy (SLNB) is a very important method in detecting lymph nodes metastasis. There are several methods developed to detect sentinel lymph node. In this study, we will research on sentinel lymph node biopsy (SLNB) by using Chinese ink and study on its feasibility, clinical value and suitable concentration. Methods: Forty-two female rabbits were randomly divided into seven groups with 12 sides of mammaries (6 animals) in each group.The second mammary and the armpit of the same side were anatomized and injected 0.1 ml different dyes (1% isosulfan blue, 0.1%, 1%, 10%, 20%, 50%, 100% sterilized Chinese ink) at the base of the second mammary. We observed the dying time of the sentinel and the second lymph nodes and the fading time of the dying nodes. The pathological and histological examination of the sentinel lymph nodes were conducted in 5 minutes,1 hour and 2 weeks after the nodes were dyed by ink, respectively. The rabbits’ hearts, lungs, livers and kidneys were detected pathologic changes. Results: There was no obvious difference among different concentration ink on the dyeing time of the sentinel and second lymph nodes (P > 0.05),but distinctively different from 1% isosulfan blue (P < 0.05). There was no obvious difference between groups on the number of the dyed nodes (P > 0.05). But the nodes dyed by 0.1% ink were dyed too lightly to be found. The average fading time of the nodes dyed by 1% isosulfan bluewas 33.9 minutes, and the nodes dyed by ink were still dyed deeply 2 weeks after the experiment. The pathologic examination showed that the carbon aggregated in the lymph nodes sinus 5 minutes after the nodes were dyed, but was phagocytosed by Macrophage (MΦ) 1 hour after dyed. The groups (0.1%, 1%, 10% ink) showed good histology image, however, groups (20%, 50%, 100% ink) showed too much carbon aggregation to disturb the observation. There were no difference in blood routine and pathologic change between these two groups. Conclusions: Chinese ink of concentration 1% to 10% is a useful dye of SLNB according chromaticity, histological observation and security. This dye had latency clinical value and was a new type of the dye for SLNB. No significant financial relationships to disclose.
Frequency of biopsies (BX) and colposcopy (CP) of intraepitelial lesions (IL) in the cervical cancer screening program (CCSP)
Authors: Holgado S. , Sanchez Segura M. , Zarba J. J. , Monroy C. , Lorente C. , Elias A. 
Published: March 2020

11000 Background: Cervical cancer is a public health problem in developing countries that can be prevent by screening programs. The loss of patients with PAP smears with IL is one of the main concern in the CCSP. The objectives of this study were establish the frequency of IL in the CCSP of Tucumán and determine the frequency of BX and CP in patients with IL within the program. Methods: Data was taken from the clinic-epidemiological charts of CCSP, and pathology reports of 29,169 cytologies (CX) done in women entered in CCSP of Tucumán between 1997 and 2004 The PAP smears were done and informed following Bethesda system and centralized in Hospital Centro de Salud: Zenón Santillán of Tucumán. Results: 2% of the CX were IL. In the beginning of program in 1997 in HSIL and LSIL a BX was performed in 22% and 18% of patients respectively and in 2004 BX was performed in 61% and 25% respectively. There were no data of CP before 2001 but in 2001 a CP was performed in HSIL and LSIL in 21% and 9% and in 2004 CP was performed in 43% and 14% respectively. Conclusion: The percentage of BX and CP performed in IL patients included in the CCSP, increased in the last year of program achieving a 60% and 43% in HSIL which is quite acceptable in a developing country. No significant financial relationships to disclose.
The power of the biomarker for cervical cancer control
Authors: Markovic N. S. , Markovic O. , Henderson E. S. 
Published: March 2020

11001 Background: At ASCO 2001, the Cervical Acid Phosphatase - Papanicolaou Test (CPT) was introduced as a biomarker-based technology as a potential in vitro diagnostic device. At ASCO 2004 and 2005, we reported results from clinical trials on 2,000 subject/specimens. In a setting of standard cervical cancer screening, the safety and effectiveness of CPT (MarkPap® Test) was compared with control Pap smear and LBP. The favorable results motivated us to expand this translational research in areas where this biomarker is crucial: self-sampling and digital evaluation. We report a pilot study designed to assess whether upgrading CPT with digital image processing (IT technology) could create a new device for an effective telecytopathology. Methods: Material: Cervical specimens self-obtained by volunteers, specimens collected in prior clinical trials (Library of MarkPap slides), and control slides. Instruments and methods: We have assembled a set of instruments and procedures to create images from microscopic slides, to convert analog into digital images, to capture and store digital images and clinical data in computer files, to transfer image files via Internet to a central server for evaluation by cytotechnologist/pathologists, and to return the reports within hours. At the end, the results of reading digital and direct images were available for comparison. Results: Since each instrument was “fit-for-use”, we have tested different “conditions-for-use” for providing digital images comparable to direct images. Images of self-sampled specimens, controls and existing slides were processed through a new setup of five modules: image acquisition, image and data transferring, image evaluation, results reporting and quality control. It was made possible by upgrading software. There was no difference between results obtained after evaluation of digital or direct images. Conclusion: Using CPT and available instruments and software, we have developed a prototype in vitro diagnostic medical device, which could permit expert evaluation of cervical specimens to be performed rapidly and at affordable cost for developing countries. This device should be able to use self-obtained specimens, field laboratory personnel and equipment, but to provide high-qualified evaluation within hours for an easy affordable cost. [Table: see text]
Combined regimen of temozolomide and liposomal pegylated doxorubicin in glioblastoma—Toxicity and efficacy
Authors: Bogdahn U. , Jauch T. , Beier C. , Beier D. , Gänβbauer S. , Glas M. , Koch H. , Wismeth C. , Steinbrecher A. , Hau P. 
Published: March 2020

11501 Background: Temozolomide (Temodar, TMZ) recently showed promising efficacy in an EORTC trial on first-line therapy of glioblastoma (Stupp R, 2005). Pegylated liposomal doxorubicin (Caelyx, PEG-DOX) was evaluated in patients with recurrent high-grade glioma and showed an overall response rate of 40% (Hau P, 2002). Therefore, a combination of both agents seems promising. Methods: TMZ was given orally 75 mg/m2 daily during standard radiotherapy (initiation) and 150–200 mg/m2 days 1–5 in 28 days starting 4 weeks after radiotherapy (maintainance). PEG-DOX was given as a short-time infusion in a dose-escalation regimen once prior to radiotherapy and on days 1 and 15 starting 4 weeks after radiotherapy. PEG-DOX was escalated for 5 mg/m2 in groups of three patients starting with 5 mg/m2 (group 1) and a highest dose of 20 mg/m2 (group 4). Results: In the dose escalation part of this study, the regime detailed above was feasible, tolerable, and able to induce objective responses and stabilizations in patients with glioblastoma. In the first treatment group (5 mg/m2 of PEG-Dox), one out of 7 evaluable patients had a dose limiting toxicity (DLT). In the second, third and fourth treatment groups, the regimen was tolerated without DLT. Concerning efficacy in the “treated-patients” analysis of 18 patients, 1 had a partial response in MRI, and 12 patients had tumor stabilization 4 weeks after conclusion of radiotherapy. Only 5 patients progressed early. Twelve patients responded with progression free survival times of 13 to 76 weeks. One patient is still progression free after 120 weeks of treatment. Conclusion: As no DLT was observed in dose group 4, MTD was not reached and we proceed to the efficacy phase of the trial with PEG-DOX in a dose of 20 mg/m2. Seventeen patients are included so far. Results will be compared to the published study EORTC 26981/22981 (Stupp R et al., 2005) which did set a new standard in the first-line treatment of glioblastoma as survival times of more than 14 months and a 2-year overall survival of 26% were reached. Regarding the promising preliminary survival data of study RNOP-09, we expect even better results with the regimen used in this protocol. [Table: see text]
High dose chemotherapy with autologous stem cell rescue (ASCR) for recurrent medulloblastoma
Authors: Diez B. , Garcia Lombardi M. , Chantada G. , Dengra C. , Fernandez Sasso D. , Koziner B. 
Published: March 2020

11507 Background: Medulloblastoma is a highly lethal disease when it recurs and very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. Methods: Between 8/97 and 8/05 14 patients (M/F 12/2) with recurrent medulloblastoma, aged 2 to 33 years (median, 10.5 years) at ASCR, were treated. Thirteen had relapsed after chemotherapy and craniospinal + posterior fossa irradiation and one after chemotherapy (Baby POG) at a median time of 19 months (7 to 148). One had a local relapse and 13 had dissemination at relapse (M1: 1, M2: 7 and M3: 5) Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/ml × min via Calvert formula) on days −8, −7, −6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days −5, −4, and −3 respectively; followed by ASCR on day 0. Results: Four patients died of treatment-related toxicities at 0, +23, +42 and +51 days post ASCR (bacterial sepsis in 2, CMV infection in 1 and CNS hemorrhage in 1). It should be remarked that all the toxic deaths were observed in patients auto grafted before October 2000. Five of 14 patients (35%) are event-free survivors at a median of 70 months post-ASCR (range: 5 to 86 months). Tumor recurred in the remaining 5 patients at a median time of 2 months post ASCR (2 to 15). All died at +23, +16, +12, +9 and +4 month post ASCR. Conclusions: Our results seem consistent with those published by Dunkel IJ (J. Clin Oncol; 16:222 - 8 1998) and argue about the efficacy of high dose chemotherapy with ASCR to provide long-term survival for some patients with recurrent medulloblastoma. No significant financial relationships to disclose.
Electrical spinal cord stimulation during radiotherapy and temozolomide in high grade gliomas. A phase II report
Authors: Clavo B. , Robaina F. , Cabezon A. , Jorge I. J. , Ponce P. , Pinar B. , Ruiz A. , Otermin E. , Hernandez M. A. , Carreras J. L. 
Published: March 2020

11510 Background: Ischemia-hypoxia in high grade gliomas (HGG) turns tumor cells more aggressive and more resistant to radiotherapy (RT) and temozolomide (TMZ). Higher glucose metabolism pre-treatment has been correlated with better response to TMZ using 18-FDG-PET. In preliminary works, we have reported that electrical spinal cord stimulation (SCS) can modify loco-regional oxygenation, blood flow and metabolism in HGG. The aim of this study was to evaluate tumor response and toxicity in HGG using SCS during RT plus TMZ. Methods: 10 patients (males/females: 8/2; median age: 51 years (30–68)) were enrolled in this trial. Tumors were 6 glioblastomas and 4 relapsed anaplastic gliomas. Diagnosis was after complete resection (1), subtotal resection (6), biopsy (1) or MRI + PET (2 relapsed HGG). Tetrapolar electrode for SCS was percutaneously inserted on the posterior surface of the cervical spinal cord at C2-C4 level. RT was at 2 Gy/fraction, 5 fractions/week, total dose 60 Gy (40 Gy in previously irradiated tumors). TMZ was administered at 75 mg/m2 daily during RT, followed by at least 6 cycles of adjuvant TMZ at 200 mg/m2. Tumor response was evaluated by CT and PET. Results: After concurrent RT+TMZ, CT showed: 5 partial response (PR), 3 complete response (CR), 2 stable disease (SD). After 6 adjuvant cycles of TMZ, CT (median 10 months after surgery) showed: 4 PR, 3 CR, 3 progression disease (PD). PET showed post-surgical residual tumor in the 9 evaluated patients. After 6 cycles of TMZ, PET showed: 4 CR, 2 PR (they obtained delayed CR after 12 and 18 cycles of TMZ), PD n = 2, and two patients without PET assessment (1 with PR in CT, and 1 without tumor in CT). For the study group median overall survival (OS) was 22 months (95% CI = 14–30) and for glioblastomas 16 months (95% CI = 6–26). For relapsed anaplastic gliomas mean OS was 37 months (95% CI = 22–52). One patient did not finish scheduled adjuvant TMZ and only one patient experienced hematological toxicity with neutropenia G-I and thrombopenia G-III. Conclusions: Electrical SCS during RT+TMZ did not increase toxicity. Preliminary data about tumor response and OS seem to be encouraging and they support further research. Supported by Grants: FUNCIS 03/09 and ISCiii, RTICCC C03/10. No significant financial relationships to disclose.
Yttrium-90-labeled ibritumomab tiuxetan for primary CNS lymphoma
Authors: Kiewe P. , Jahnke K. , Maza S. , Korfel A. , Munz D. L. , Thiel E. 
Published: March 2020

11512 Background: Salvage treatment has not yet been established in primary CNS lymphoma (PCNSL). Here we report first results of an ongoing phase II study with a single treatment course of Y-90 anti-CD20 antibody ibritumomab tiuxetan in relapsed/resistant PCNSL. Methods: Eligibility criteria include histologically confirmed, recurrent PCNSL after at least one prior treatment, HIV negativity and adequate bone marrow and cardiac function. Primary endpoint is overall response, secondary endpoints are response duration, survival, and toxicity including late neurotoxicity. Treatment includes rituximab 250 mg/m2 on day -7 and day 0, followed by Y-90-ibritumomab tiuxetan 15 MBq/kg IV. Response evaluation by contrast-enhanced magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) is scheduled before, one month and two months after treatment as well as every three months thereafter in responders. In two patients single photon emission computed tomography (SPECT) target imaging with gamma-emitting 111-Indium-ibritumomab tiuxetan was performed repeatedly. Results: To date, four patients have been enrolled. Complete response on MRI and decreased but still detectable FDG-uptake in PET was seen in one patient; the response duration was one month. In another patient uncertain complete response with minimal residual contrast enhancement lasting 12+ months was observed. Two patients had disease progression. One patient developed CTC grade 3 pneumonia during CTC grade 2 leukopenia, two patients had CTC grade 3 thrombocytopenia lasting up to 6 weeks. SPECT indicated target accumulation in the tumor starting 48 hours and still ongoing 7 days after injection of 111-Indium-ibritumomab tiuxetan. Conclusions: This is the first report on a successful treatment of PCNSL with Y-90-ibritumomab tiuxetan and penetration of a therapeutic antibody into PCNSL, warranting further investigation. No significant financial relationships to disclose.