bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunity to MUC1 in pancreatic and breast cancer
Authors: Geller B. A. , Lepisto A. J. , Ahrendt G. M. , Finn O. J. , Ramanathan R. K. , Brufsky A. M. 
Published: March 2020

21166 Background: A cancer vaccine composed of MUC1 loaded DCs was effective at inducing tumor rejection in MUC1 transgenic mice. We present data from a phase IB clinical trial of the same vaccine in patients with pancreatic cancer. Preliminary analysis of this trial was reported at ASCO 2004,# 2578. Our current studies based on the results of this trial explore the importance of anti-MUC1 immunity in patients with early breast cancer, aiming to create a strong rationale for boosting these responses with vaccination in adjuvant settings. Data from both studies will be presented. Methods: The objectives of the vaccine trial were to evaluate toxicity of the vaccine, its ability to boost immunity and clinical outcome. Patients received autologous DC loaded with MUC1 100mer peptide every 3 weeks for a total of 3 doses and a booster dose 6 months later. Blood samples were obtained prior to each dose and at various times post vaccination. For the current study, 100 preoperative/pretreatment peripheral blood samples have been collected prospectively from patients with early breast cancer. Multiple immune parameters are being assessed in each group. Results: Data from extensive immune response analyses of the pancreatic cancer vaccine will be presented in detail at AACR 2007, and summarized here to provide the basis and comparison for our ongoing studies in early breast cancer. 4/12 patients in the vaccine study are alive without recurrence at three years. Even though effector and regulatory T cell responses were detected in several patients, none could be correlated with long-term survival. Several patients had anti-MUC1 antibody responses that remained stable following vaccination, which also did not correlate with survival. Ongoing studies in early breast cancer are assessing the potential differences in the quality of anti-MUC1 responses between early and late stage disease. Conclusions: In the setting of advanced disease, such as pancreatic cancer, the vaccine appears to have an effect on keeping regulatory T cells low and cellular and humoral immunity stable, without causing any significant toxicity. Ongoing studies in early breast cancer are aiming to define the immune parameters that might predict increased survival. No significant financial relationships to disclose.
Molecular subsets of male breast carcinoma in southern Brazil
Authors: Graudenz M. S. , Silva L. M. , Toscani N. V. , Freitas A. M. , Caleffi M. 
Published: March 2020

21167 Background: Molecular profiling can identify subsets of breast cancers with different tumor behavior. There is few data regarding breast cancer in males, since it's an uncommon disease, accounting for less then 1% of all malignancies in man. Treatment and prognosis are often extrapolated from female breast cancer, but differences and/or similarities between these two diseases are not well established. The aim of this study is to report the molecular profile defined by immunohistochemistry (IHC) of male breast carcinoma (MBC) in southern Brazil. Methods: We reviewed 25 cases of MBC diagnosed between January 1993 and December 2006. Retrieved data included disease stage, tumor grade, size, and lymphnode status. IHC was performed with the following primary antibodies: ER (Novocastra), Cytokeratin 5/6, Cytokeratin 8/18 (DAKO, Carpinteria, CA), HER1 (DAKO) and HER2 (CB11 clone, DAKO). Results were scored by IHC according to established criteria in the literature. The study was approved by the institutional Ethics Committee. Results: Patient's median age at diagnosis was 66 years-old (44–84 yrs). All cases were invasive ductal carcinoma of no special type except for one lobular carcinoma. Median tumor size was 2.5cm (0.6–5.2cm). IHC was performed in 17 cases. The overall frequency of ER positivity was 82% (14/17); CK5/6 11.8% (2/17); CK8/18 94.1% (16/17); HER1 23.56% (4/17) and HER2 17.6% (3/17). Using the whole panel of antibodies we determined that 11 cases (64.7%) were of the ER+/luminal phenotype, 3 (17.6%) of the HER2 overexpressing, 2 (11.7%) of the normal breast like and 1 (5.9%) tumor of the basal phenotype (HER1+ and CK5/6-). Conclusions: Male breast carcinoma presents similar expression profiling frequencies to that of female breast carcinomas. To our knowledge, this is the largest series of male breast cancer ever studied in Brazil. Despite intrinsic gender differences, breast carcinoma may share common tumor biology characteristics in males and females. No significant financial relationships to disclose.
Linking diet, religion and cancer
Authors: Yadav S. P. , Sachdeva A. 
Published: March 2020

21172 Background: Consumption of onion and garlic has been shown to give protection against various cancers. Motivated by this observation we intended to look at the cancer incidence in a population belonging to Jain religion that does not consume garlic and onion due to religious belief. This study was done to see cancer incidence in children of Jain religion as compared to other religions at a single centre. Methods: It was a retrospective analysis of consecutive children less than 16 years of age diagnosed with cancer at Sir Ganga Ram Hospital from January 2005 to January 2007. We excluded adult patients with cancer as tobacco and alcohol consumption in this age group would have been confounding factors.Age, sex and religion were noted. Data from Census of India for year 2001 was used to know distribution of various religions in general population alongwith literacy rates and proportion in 0–6 years age. Results: As per 2001 Census of India , distribution of population in India as per various religions is Hindu 80.5%, Muslim 13.4%, Christian 2.3%, Sikh 1.9%, Buddhist 0.8% , Jain 0.4% and others 0.6%. Proportion of population in 0–6 year of age in India is 15.9% and as per religions Hindu 15.6%, Muslim 18.7% ,Christian 13.5%, Sikh 12.8%, Buddhist 14.4% and Jain 10.6%. Literacy rates of India is 64.5% and by religion is Hindu 65%, Muslim 59.1% Christian 80.3%, Sikh 69.4%, Buddhist 72.7% and Jain 94%. Distribution of population in Delhi as per various religions is Hindu 82%, Muslim 11.7%, Christian 0.9%, Sikh 4%, Buddhist 0.2% and Jain 1%. Total of 201 patients were diagnosed with cancer and distribution as per religions was Hindu 162 (81%), Muslim 15 (7.5%), Christian 3 (1.5%), Sikh 8 (4%), Buddhist 1 (0.05%) and Jain 12 (6%). Conclusions: Incidence of cancer in children of different religions is similar to that of proportions of population of different religions in Delhi except for Jain religion where incidence of cancer is 6 times higher despite lesser number children in 0–6 year in this population as compared to other religions . Major difference is the diet lacking in onion and garlic . Other reason could be increased literacy levels in Jain community . This link between diet ,religion and cancer in Jain population needs to be studied in a larger muticenteric setting as it has implications for the whole world. No significant financial relationships to disclose.
Breast cancer HER-2 amplicon-associated targets for immunotherapy identified by gene array analysis
Authors: Kostyal D. , Shay T. , Lanning C. , Horton K. , Welt S. , Whelle S. 
Published: March 2020

21174 Background: Gene array technology was used to investigate Trastuzumab (T) induced molecular expression patterns in HER/2 amplified breast cancer cell lines. A variety of over-expressed and aberrantly expressed proteins were identified. Further analysis of these data demonstrated potential candidate target proteins for T-cell immunotherapy. The advantages of utilizing gene array analysis to identify target proteins for immunotherapy include rapid data generation and analysis, statistical confidence and reproducibility. Methods: BT 474 and SK-BR3 breast cancer cell lines contain the HER/2 amplicon. Under growth conditions demonstrating inhibitory effects of T (0.25–50 micrograms/ml), RNA extracts from treated and untreated cells were analyzed and compared by whole human genome, gene array analysis. Results: Three sperm associated proteins were found to be expressed in these breast cancer cell lines. In comparison to the HER/2 expression, sperm associated antigen-1 (saa-1) was found to be expressed at very high levels, approximately 30–40% the level of HER/2. Furthermore, treatment of breast cancer cell lines with T did not reduce the level of saa-1 expression. Two other aberrantly expressed genes were also identified, sperm associated antigen 8 (saa-8) and sperm associated antigen-14 (saa-14). Unlike saa-1, both saa-8 and saa-14 expression were down regulated by T treatments. Conclusions: Breast cancer patients with HER/2 over expressing tumors have a poorer prognosis. T treatment is an important part of the clinical management of these patients especially early in their course. The immunotherapy targets described here may further improve outcomes of T treatments and for T resistant disease when utilized as vaccines. These proteins are components of sperm acrosomes and whether they play a role in invasion and metastases is under investigation. No significant financial relationships to disclose.
Targeted immunotherapy with intentionally mismatched rIL-2 activated donor lymphocytes in an attempt to eliminate minimal residual disease in patients with high-risk metastatic cancer
Authors: Slavin S. , Or R. , Dray L. , Samuel S. , Ackerstein A. , Shapira M. Y. , Resnick I. B. , Bitan M. , Morecki S. 
Published: March 2020

21175 Background: Graft-versus-leukemia and graft-versus-tumor (GVT) effects following stem cell transplantation are well established, however, procedure related toxicity and mortality are unavoidable. In addition to limited efficacy following stem cell transplantation (SCT), graft-versus-host disease (GVHD) is unavoidable. Our protocol was designed to induce more potent anti-cancer immunotherapy by rIL-2 activated intentionally mismatched donor lymphocytes (MDL) at the stage of minimal residual disease (MRD) outpatient procedure with no SCT avoiding GVHD. Methods: Optimizing MDL was accomplished by cyclophosphamide 1,500 mg/m2 and 2 injections of alpha interferon (3x106IU) for more effective immunotherapy, aiming for depletion of regulatory T cells, followed by infusion of haploidentically mismatched lymphocytes activated with rIL-2 (6,000 IU/ml) for 4 days. On the day of cell infusion, patients received rIL-2 6x106 IU subcutaneously outpatient for 5 days. Results: A total of 41 (age 5–73, median 52) high risk patients were included: metastatic breast 13; colorectal 3; gastric 3; pancreatic 3; melanoma 3; head & neck 3; glioblastoma 2; and 6 with other solid tumors. Five patients had resistant hematological malignancies: multiple myeloma 2; non-Hodgkin's lymphoma 2 and Hodgkin's disease 1. 6 patients received lymphocytes with bispecific antibodies for targeted cell-therapy (3 with catumaxomab against CD3 & epithelial cell adhesion molecule (EpCAM); 3 with ertumaxomab directed against CD3 & Her-2/neu WHO toxicity >grade 2 was noted. 14 of evaluable patients are alive. 10/32 with solid tumors are alive, 7 with no evidence of disease > 9–91 (median 17) months (4 breast; 1 squamous cell; 1 head & neck; 1 prostate). Of 5 patients with hematological malignancies 4 are alive and disease free >18–96 (median 46) months. Conclusions: Safe induction of GVT effects may be accomplished by MDL, preferably targeted with bispecific antibodies after cyclophosphamide conditioning lymphocytes are more potent and act faster than matched lymphocytes and GVHD is avoided by rejection of donor lymphocytes. When applied at a stage of MRD, such treatment may result in operational cure. No significant financial relationships to disclose.
Symptoms or signs due to different chemotherapeutics and their relationship with serum cytokines/VEGF levels in patients with cancer
Authors: Demirkazik A. , Yilmaz H. , Akbulut H. , Yalcin B. , Icli F. 
Published: March 2020

21176 Background: Several problems such as myalgia, arthralgia, fever, dyspnea, generalised edema and pleural effusion and rarely “systemic capillary leak syndrome” may appear following the chemotherapy in cancer patients. Although it is supposed that some cytokines are associated with the development of these problems, there is no clear evidence for the relation between the cause and the effect. In this study, the relation between some symptoms following the first chemotherapy in cancer patients and the serum levels of interleukin-2 (IL- 2), interleukin-11 (IL-11), tumor necrosis factor alpha (TNF-a) and vascular endothelial growth factor (VEGF) which are supposed to cause these symptoms was investigated. Methods: Forty-four (28 male and 18 female) patients with cancer who had no heart, lung or renal diseases were consecutively enrolled to this study. Twenty-nine patients (27 with lung cancer, 1 with locally advanced gastric and 1 with pancreatic carcinoma) had active tumors. Fifteen patients (11 with breast cancer, 2 with gastric carcinoma, 1 with colon carcinoma, 1 with ovarian cancer) had no tumor because they were just curatively operated. Patients’ symptoms and findings due to chemotherapy were noted just before the chemotherapy and 24 hours later following chemotherapy. Patients’ serum samples were taken for the measurement of VEGF, TNF, IL-2 and IL-11 levels. Results: Any relation between the chemotherapeutic drugs and the symptoms or findings such as edema, dyspnea, cough and flu-like syndrome in patients were not observed. Otherwise, there were no relation with response to the chemotherapy and serum levels of VEGF, TNF, IL-2 and IL-11. But, patients who were not treated with paclitaxel, docetaxel, gemcitabine and vinorelbine showed a significant decrease in their IL-11 levels (p: 0.006). Conclusions: There was no statistically important difference between chemotherapeutics in terms of cytokine related effects. Although, there was no relation with response to the chemotherapy and serum cytokine levels, serum IL-11 levels were stable in patients administered with paclitaxel, docetaxel, gemcitabine and vinorelbine when compared with other drugs. No significant financial relationships to disclose.
Relevance of modified prognostic score for breast carcinoma on fine needle aspiration cytology in a resource-poor setting
Authors: Malami S. A. , Sahabi S. M. 
Published: March 2020

21177 Background: Breast cancer is the commonest malignancy in premenopausal Nigerian women in whom it is almost uniformly fatal probably due to lack of access to early diagnosis and treatment. To enhance the value of fine needle aspiration cytology, a rapid and comparatively new technique in our center, we sought to verify if it is also a cost-effective test to predict biological behavior in breast carcinoma. We developed a modified grading system to compare the cytologic features of the cases in our series with known prognostic factors (tumours size, histologic grade and axillary lymph node status) in subsequently excised tissues. Methods: Fine needle aspirates obtained in 42 patients diagnosed as ductal cell carcinoma not otherwise specified (NOS) at the UDUTH Hospital, Sokoto, Nigeria were investigated. The three cytologic features used were nuclear grade (score 1–3), cellular dyscohesion (score 1–3), and bare atypical nuclei (score 0, 1). A cytological score of 3 and below was considered a low score, and a score of 4–7 was considered a high score. We also categorized each patient according to the Nottingham Prognostic Index (NPI) into: good prognostic group (GPG), moderate prognostic group (MPG) and poor prognostic group (PPG). The cases in GPG and MPG were considered to belong to a more favourable category. Results of cytoprognostic scores were compared with the respective pathological information calculated by the NPI. Results: Eighteen of the 20 cases that had a cytologically high score were confirmed to be PPG while 2 correlated with MPG. Among the 22 cases that had cytologically low scores 14 cases were not correlated with favourable NPI index (belonged to PPG category) while the remaining 8 correlated well (MPG = 4 and GPG = 4). The overall accuracy for cytologic grading was 62% (26 out of 42 cases). Conclusion: Tumour typing on FNA material correlates with the NPI in the poor prognostic group. However, this modified cytoprognostic score seems to have doubtful promise as a prognostic factor in our group of patients with favourable NPI. The importance of each cytological feature used in this grading system will be determined by regression analysis in a larger sample size. No significant financial relationships to disclose.
Improvement in quality of life and symptom control with MYCOBACTERIUM W (CADI-05) in head and neck cancer
Authors: Dave R. I. , Tripathi U. B. , Parikh B. J. , Patel K. M. , Shukla H. K. 
Published: March 2020

21186 Background: Recurrent, radiated and chemotherapy given patients are having many unmanageable symptoms and problems. This condition is worsened by malnutrion, infection, pain and immuno suppression. Modifying immune mechanism of the body is the last and best weapon to fight against such diseases. Role of immunotherapy in the treatment of malignant diseases is on experimental level. Dr George Thyphrontis & Michael Kousilers have produced good results in carcinoma of urinary bladder, melanoma & lung cancer with Immunotherapy. At GCRI, we have tried vaccine, prepared from mycobacterium-W in 100 cases of Head & Neck Cancer. Methods: As a prospective nonrandomized study, to see beneficiary effect on quality of life and symptom control, we have done a trial during Jan. 2004 to Dec.2005. Informed consent and ethical clearance was obtained. Study was made to find out any side effect or adverse reactions of the vaccine. After fulfilling the criteria of inclusion and exclusion the case was selected for study and 0.1 ml vaccine (CADI-05) was injected intradermally with all aseptic precautions. Four injections, weekly and later on four injections monthly were given. Patient was followed up for 6 months. Results: Total No. of cases -100. M / F - 89/11. age distribution - Maximum No. were in 5th decade -(34%) followed by 6th decade (21%)Site of primary - Commonest site was Buccal mucosa (29%) followed by tongue (17%). There was no major side effect. Only 5% Patients developed constitutional symptoms and infection at injection site. 27% patients had pain relief. Symptom control was seen in 15% patients. Improvement in quality of life was observed in 82% of patients. 4% of patients had no effect. The beneficiary effect lasted for three month in 27% patients and more than six months in 13% patients. The effect was more marked in dysphagia, ulcer and fistula. Effect was insignificant in strider, change in voice and metastatic nodes. Four patients are living with Immuvac in spite of disease symptom free for more than one year. Conclusions: Immunotherapy with Mycobacteium W can safely be used to improve quality of life and control of symptom in terminally ill Head & Neck cancer. No significant financial relationships to disclose.
Evaluation of occurence of cancer of the lung among young people in six regions of the western Ukraine
Authors: Kitsera N. , Shparyk J. 
Published: March 2020

21188 Background: Analysis of the cases of malignant lung tumors of young people (<34 yrs, born in 1963–2004) and diagnosed in 1997–2004 was made using the materials of the database of cancer registers of Volyn (V), Ivano-Frankivsk (IF), Lviv (L), Rivne (R), Ternopil (T) and Chernivtsi (C) regions. The population of young people <34 yrs of this region - 4.2 million/year. Results: Among 7541 cases of cancer in the six regions of the Western Ukraine malignant tumors of the lungs were diagnosed in 102 cases (1.4%). This pathology was registered in males in 57 cases, and in females in 45. The number of males with tumors of the lungs prevailed in V, IF, L, T. The number of young males and females with such pathology during the said period was the same - 11 cases in each gender group - in R. The youngest among the 102 individuals from the above said six regions were a boy aged 6 and a girl aged 16 from R. Combination with other tumors was observed in three females (C49, C53, C58) and one male (C81). In C among 766 cases of malignant tumors in young people <34 years lung cancer were detected in 5 (0.7%). Among 959 cases of cancer such tumors of the lungs were detected in 8 (0.8%) in V. Among the young people <34 years this pathology was detected in 14 (1.2%) in IF out of all 1156 cases of malignant tumors, in T - 947 tumor - 15 cases (1.6%). Among the six above regions in L there have been detected 2465 cases of malignant tumors, of which lung cancer were diagnosed in 38 - 1.5%. The highest frequency of occurrence of this pathology was registered in R (1.8%) - 22 cases in 1248 cases of malignant tumors. Conclusions: Fluctuation of frequency of this pathology in all these regions in various years during the investigated period had a wave-like character. As each of these regions is characterized by different geographic and climatic conditions, physical and chemical factors, exhausts of industrial enterprises, the study of frequency of malignant tumors in young people will permit to evaluated more objectively contribution of hereditary factor in the development of this pathology. The perspectives of further research in this field lie in the study of the role of genetic predisposition to the occurrence and development of malignant tumors in each patient, taking into account ecological zone of residence, occupational hazards and harmful habits. No significant financial relationships to disclose.
A phase I dose escalation safety and pharmacokinetic (PK) study of SSR244738 administered as a one-hour intravenous (IV) infusion every 3 weeks in patients (pt) with refractory solid tumors
Authors: De Braud F. G. , Isambert N. , Curigliano G. , Spitaleri G. , Ferrant E. , Ramazeilles C. , Bolloni L. , Fumoleau P. 
Published: March 2020

2518 Background: This phase I study of SSR244738, a G2-cell cycle inhibitor cytotoxic agent, was aimed to establish the dose limiting toxicities (DLT), the maximum administered dose (MAD) and to characterize the PK profile of the proposed schedule. Methods: SSR244738 was administered as one-hour IV infusion every 3 weeks in pts (selected according common phase I criteria) starting with a modified accelerated dose escalation scheme. PK profiles (up to day 8) were obtained in each pt after the 1st administration. CYP2C9 and CYP3A5 genotypes were analyzed to identify pts’ metabolizer status. Results: 2 centers enrolled 14 heavily pretreated pts: 5 females, 9 males, median age: 52 years (32–67), ECOG PS: 0 (93% pts); main tumor types: head and neck, lung, melanoma, and breast. 40 cycles (median = 2, range: 1–11) were administered in 6 dose levels (DL) ranging from 165 to 1,300 mg/m2. Accelerated dose escalation was stopped at 660 mg/m2 for non-proportionally increase of PK parameters respect to the dose administered . SSR244738 was well tolerated up to 1,300 mg/m2: one DLT (abnormal liver function tests ALFT) was reported in one breast cancer pt with liver metastases. Only one pt (hepatocarcinoma) was withdrawn from the study due to toxicity (ALFT) after 3 cycles at 1,000 mg/m2. 2 stable diseases were reported. PK data: mean T1/2 of 23h (range: 9.20–127), mean Vss: 11.1 L (6.43–15.8) and mean Clearance (CL): 0.71 L/h (0.041–1.43). This large variability of the CL (CV% =63%) could in part be explained by CYP2C9 genotype: so far CL is <0.4 in 2 poor metabolizers (PM) and >0.6 in extensive metabolizers. Conclusion: Due to the high CL variability, 1300 mg/m2 is considered as the MAD. 3 pts will be accrued at 1,300mg/m2 to complete the DL (a reduced dose will be given to CYP2C9 PM). Weekly and twice-weekly schedules will be tested. No significant financial relationships to disclose.