tbuckley/cabot-search huggingface dataset:
Molecular markers associated with response and clinical outcome to cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer (BOND2)
Authors: M. Azuma, D. Yang, M. Carpanu, E. Hollywood, M. Lue-Yat, W. Zhang, K. D. Danenberg, P. V. Danenberg, L. Saltz, H. Lenz
Journal: Journal of Clinical Oncology (2007)

4113 Background: Phase II (BOND2) trial of Cetuximab/Bevacizumab/Irinotecan (CBI) vs Cetuximab/Bevacizumab (CB) has shown that bevacizumab added to the efficacy of cetuximab and cetuximab/irinotecan in irinotecan-refractory bevacizumab-naïve CRC patients. We tested whether expression levels of genes involved in angiogenesis (VEGF, IL-8), the EGFR pathway (EGFR, COX2) and DNA repair (ERCC1) are associated with clinical outcome. Patients and Methods: This randomized phase II trial enrolled 81 patients. Treatment plan as: Arm A received IRI at the same dose and schedule as last received prior to study, plus Cetuximab 400 mg/m2 loading dose, then weekly at 250 mg/m2, plus Bevacizumab 5 mg/kg given every other week. Arm B received the same as arm A, but without IRI. FFPE samples for 35 out of 81 patients (M:W 24:11, median age 56 (29–80) enrolled in the BOND2 study were tested. Patients received either with CBI (n=18, Arm A) or with CB (n=17, Arm B). FFPE tissues were dissected using laser-captured microdissection and analyzed EGFR, ERCC1, VEGFA, VEGFR2, COX2, Cyclin D1, IL-8, and NRP1 mRNA expression using a quantitative real-time RT-PCR. Gene expression values are expressed as ratios between the target gene and internal reference gene. Results: All eight genes and treatment arm were considered in the CART analysis. The classification tree for response, progression-free survival, and overall survival are evaluated. The expression levels of VEGFR2 and NRP1 classified patients in 3 response groups with response rate range from 61% to 0%. Patients who were classified as responders (Group I; VEGFR2=0.65 and NRP1&lt;2.285) were at a lower risk for progression, compared with patients who were classified as non- responders (Group II; VEGFR2=0.65 and NRP1=2.285 and Group III; VEGFR2&lt;0.65). The expression levels of NRP1 and ERCC1, and EGFR and VEGFR2 were chosen to classify patients into 3 groups with distinct risk of progression-free survival and overall survival, respectively. Conclusion: These data suggest that gene expression levels may be molecular markers of response for patients with mCRC treated with CBI or CB. Prospective studies are needed to validate these preliminary findings. No significant financial relationships to disclose.
Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.
Authors: D Osoba, B Zee, J Pater, D Warr, J Latreille, L Kaizer
Journal: Journal of Clinical Oncology (1997)

To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables.Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV.Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors.Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.
Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking
Authors: Mohamed Saeed, Thomas Efferth, Onat Kadioglu, Hassan Khalid, Yoshikazu Sugimoto
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Natural products have been extensively studied and involved in cancer therapy field [[1][1]], apigenin has considerable cytotoxic activity in vitro and in vivo. Despite many mechanistic studies, less is known about resistance factors hampering apigenin's activity. We
Epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab and bevacizumab as neoadjuvant therapy for HER2-positive locally advanced breast cancer (LABC) or as adjuvant therapy for HER2-positive pathologic stage III breast cancer (PS3BC): A phase II trial of the NSABP Foundation Research Group
Authors: J. W. Smith, M. Buyse, P. Rastogi, C. Geyer, S. Jacobs, E. Patocskai, N. Wolmark
Journal: Journal of Clinical Oncology (2009)

580 Background: A previous phase II study evaluating the combination of trastuzumab (tras) and bevacizumab (bev) as first-line therapy in HER2 + MBC showed a response rate of 54%. The purpose of this trial is to determine the cardiac safety profile of these agents with docetaxel (T) following epirubicin plus cyclophosphamide (EC) in women with LABC and PS3BC and the activity in those with LABC. Methods: Since June 2007, 75 women with HER-2 + LABC or PS3BC have begun epirubicin 90 mg/m2 IV plus cyclophosphamide 600 mg/m2 IV q3wks x 4 followed by docetaxel 100 mg/m2 IV q3wks x 4. Targeted therapy: Cohort A (neoadjuvant), bev 15 mg/kg IV with Cycle 4 of EC, continued with the first 3 cycles of T. Standard weekly tras with 4 cycles of T. Postop, bev 15 mg/kg IV and tras 6 mg/kg IV q3wks to complete 1 yr of targeted therapy. Cohort B (adjuvant), bev 15 mg/kg q3wks for 4 cycles and weekly tras with T. After chemotherapy, bev and tras q3wks to complete 1 yr of therapy. Primary endpoints were the rate of cardiac events in both cohorts and pCR rate in breast/axillary lymph nodes in Cohort A. Results: Median age was 50 yrs. In Cohort A, 28 (53%) patients (pts) were stage IIIA, 20 (38%) stage IIIB, and 5 (9%) stage IIIC. 13 (25%) had inflammatory BC. A pCR occurred in 19 of the first 36 pts (53%). Toxicity information on the first 73 pts in both cohorts showed that grade 2 LVEF dysfunction has developed in 5 pts and grade 3 LVEF dysfunction in 2, 1 with NYHA Class II and 1 with Class III symptoms. The latter met criteria for a cardiac event. Conclusions: The regimen is active with an acceptable preliminary rate of cardiac toxicity. Updated results will be presented. This trial is conducted with the support of Genentech. [Table: see text]
Abstract LB-299: Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells
Authors: Adi Gilboa-Geffen, Peter Hamar, Lee Adam Wheeler, Radiana Trifonova, Fabio Petrocca, Anders Wittrup, Judy Lieberman
Journal: Cancer Research (2015)

Abstract Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (T-IC, also known as cancer stem cells). Here we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knockdown gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosphere formation (in vitro T-IC assays) and tumor initiation by EpCAM+ luminal and basal-A triple negative breast cancer (TNBC) cell lines, but not EpCAM- mesenchymal basal-B TNBCs, in nude mice. Subcutaneously administered EpCAM-AsiCs concentrate in EpCAM+ Her2+ and TNBC tumors and suppress their growth. Thus EpCAM-AsiCs provide an attractive approach for treating epithelial cancer. Note: This abstract was not presented at the meeting. Citation Format: Adi Gilboa-Geffen, Peter Hamar, Lee Adam Wheeler, Radiana Trifonova, Fabio Petrocca, Anders Wittrup, Judy Lieberman. Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-299. doi:10.1158/1538-7445.AM2015-LB-299
The value of bronchoalveolar lavage in the diagnosis and management of small airway disease
Authors: Jun Kanazawa, Takefumi Saito, Mariko Nakazawa, Kazutaka Fujita, Hirofumi Sakurai, Kenji Nemoto, Shih-Yuan Lin, Takio Takaku, Kenji Hayashihara
Journal: European Respiratory Journal (2014)

Background: Cytologic examination of bronchoalveolar lavage (BAL) provides a microscopic feature on the inflammatory status of small airway disease (SAD) as well as interstitial pneumonia. The purpose of this study is to investigate the usefulness of BAL evaluation in SAD.  Methods: Twenty-three subjects (male/female = 6/17, age 40-81 years) with suspected SAD who underwent lung function testing and chest computed tomography (CT) were enrolled. They had slightly obstructive impairment in pulmonary function testing and obstruction of the bronchioles detected indirectly by CT as a mosaic attenuation pattern of the lung parenchyma. We performed BAL with instillation of saline (50 mL, three times) into the airways and examined cellular composition in BAL fluid microscopically. In each case, the result of BAL was evaluated, based on clinical diagnosis and therapeutic effect of SAD.  Results: Eighteen patients had increased number in BAL cells. Four patients had an increase in eosinophils (10-73%), eleven patients in lymphocytes (28-90%) and three patients in neutrophils (67-90%). Five patients, however, showed normal range in both BAL cells and leucocyte differentiation. BAL cell differentiation in the first, second and third sample enabled us to differentiate between the location of bronchial and bronchiolar disease.  Conclusion: The cases with similar history, radiographic findings and lung function often showed different cellular composition in BAL. We conclude that a likely diagnosis of SAD might be reached, when BAL is combined with clinical history, CT, laboratory data and lung function. BAL evaluation might have a strong impact on treatment decisions.
Effect of Quadrivalent Human Papillomavirus Vaccination on Oral Squamous Cell Papillomas
Authors: Nika Cyrus, Adam B. Blechman, Matthew Leboeuf, Elizaveta A. Belyaeva, Maurits N. C. de Koning, Koen D. Quint, John J. Stern
Journal: JAMA Dermatology (2015)

Cutaneous verruca vulgaris lesions (warts) and oral squamous cell papillomas are common lesions caused by human papillomavirus (HPV). Multiple reports have described cases of wart resolution following quadrivalent HPV vaccination. We report the case of a patient with chronic oral papillomas with resolution after quadrivalent HPV vaccination and perform a review of the literature.An immunocompetent man in his 60s presented with chronic verrucous papules on the lips, tongue, and buccal mucosa refractory to multiple excisions. Biopsy showed squamous cell papilloma, and DNA sequencing revealed HPV-32. He received the quadrivalent HPV vaccine resulting in clearance of all lesions after 3 months. We found 8 reported cases of disseminated, recurrent warts with resolution after quadrivalent HPV vaccination. Improvement was seen within 4 weeks of vaccination, and resolution after 3 to 8 months.We report the case of recurrent oral papillomas caused by HPV-32 with complete resolution after quadrivalent HPV vaccination and reviewed reports of resolution of recalcitrant and disseminated warts after vaccination. Production of cross-protective immunoglobulins and cytotoxic T cells is a possible mechanism. There remains a critical need for randomized clinical trials to assess efficacy of quadrivalent HPV vaccination for treatment of oral squamous papillomas and cutaneous verruca vulgaris.
Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial
Authors: Michael T White, Robert Verity, Jamie T Griffin, Kwaku Poku Asante, Seth Owusu-Agyei, Brian Greenwood, Chris Drakeley, Samwel Gesase, John Lusingu, Daniel Ansong, Samuel Adjei, Tsiri Agbenyega, Bernhards Ogutu, Lucas Otieno, Walter Otieno, Selidji T Agnandji, Bertrand Lell, Peter Kremsner, Irving Hoffman, Francis Martinson, Portia Kamthunzu, Halidou Tinto, Innocent Valea, Hermann Sorgho, Martina Oneko, Kephas Otieno, Mary J Hamel, Nahya Salim, Ali Mtoro, Salim Abdulla, Pedro Aide, Jahit Sacarlal, John J Aponte, Patricia Njuguna, Kevin Marsh, Philip Bejon, Eleanor M Riley, Azra C Ghani
Journal: The Lancet Infectious Diseases (2015)

BackgroundThe RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014.MethodsUsing data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time.FindingsRTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be long-lived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity.InterpretationAnti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered.FundingUK Medical Research Council.
Countries should raise taxes on tobacco, says WHO
Authors: Anne Gulland
Journal: BMJ (2015)

Countries are urged to impose higher taxes on tobacco products, after a World Health Organization report found that only 10% of the world’s population lived in countries where tax accounted for 75% or more of the price of a packet of cigarettes.1

Thirty three countries impose taxes that account for more than three quarters of the price of a packet of cigarettes, one of the measures recommended in WHO’s Framework Convention on Tobacco Control. Raising taxes is the least implemented measure in WHO’s six point action plan on curbing tobacco …
Outcomes of therasphere radioembolization for neuroendocrine metastases.
Authors: Andrea M. Abbott, Sarah E. Hoffe, Jonathan R. Strosberg, Khaldoun Almhanna, Benjamin Biebel, Junsung Choi, Ghassan El-Haddad, Bela Kis, Jennifer Sweeney, William J. Fulp, Ravi Shridhar
Journal: Journal of Clinical Oncology (2015)

371 Background: Neuroendocrine tumors (NET) are a rare group of tumors with variable biologic activity that have a propensity for hepatic metastases. Complete surgical resection or debulking is the standard of care while chemotherapy is reserved for unresectable disease. However, liver directed therapy utilizing radioembolization with yttrium-90 (y90) may offer an alternative modality of treatment to patients with unresectable hepatic disease while minimizing systemic toxicity and providing acceptable overall survival (OS). Methods: A retrospective review of all patients undergoing y90 microsphere treatment for metastatic NET (mNET) from 2009-2013 was conducted. Patient, treatment, and post-treatment variables from initial diagnosis and y90 treatment were collected. Multivariable analysis (MVA) of factors related to OS and treatment toxicity was performed by the Cox proportional hazard model using Wald test and OS estimates were calculated using the Kaplan-Meier method. Results: We identified 74 patients with a median follow-up of 21 months. Median and 2 year OS was 26 months and 56%. Tumor burden was a significant predictor of survival. Two year OS for patients with ≤ 25%, 25-50%, 50-75%, and &gt;75% tumor burden was 63%, 59%, 40%, and 34%, respectively (log-rank p = 0.027). MVA revealed that female gender and higher disease burden were associated with increased mortality; age, location of primary tumor, resection status of the primary tumor, prior chemotherapy, and presence of extrahepatic metastases at the time of treatment were not significant predictors of OS. The majority of patients (88%) experienced a treatment related toxicity; however 72% were Grade 1/2 and only 16% were Grade 3/4. Male gender and prior liver therapy were associated with higher rates of toxicity. Conclusions: Y90 was associated with acceptable OS with minimal severe morbidity in this series of patients with mNET. Lower tumor burden and male gender were associated with better OS. These results suggest that y90 may be a potential treatment alternative for patients with unresectable mNET. Prospective studies evaluating y90 in the treatment of unresectable chemo-refractory mNET are needed.
Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer.
Authors: J Isola, S Weitz, T Visakorpi, K Holli, R Shea, N Khabbaz, O P Kallioniemi
Journal: Journal of Clinical Oncology (1993)

PURPOSE Increased expression of the lysosomal protease cathepsin D (CD) has been implicated in the metastatic progression of breast cancer. This study was designed to determine the prognostic significance of CD expression in axillary node-negative (ANN) breast cancer. The relationship of CD expression and onset of soft tissue recurrences and visceral metastatases was also studied. PATIENTS AND METHODS We analyzed a population-based group of 262 ANN breast cancer patients, none of whom had received any adjuvant chemotherapy or endocrine therapy. An immunohistochemical method based on a new monoclonal antibody (1C11) with a distinct epitope specificity made it possible to study CD expression from archival paraffin-embedded specimens and to distinguish staining in tumor cells from the high-level expression found in tumor-infiltrating macrophages. RESULTS High-level CD expression, as defined by cytoplasmic immunoreactivity in greater than 10% of the cancer cells, was found in 95 cases (36%). High-level CD expression was associated with large primary tumor size (P = .014), but not with histologic grade, estrogen and progesterone receptors, DNA index, or S-phase fraction, or with c-erbB-2 and p53 overexpression. Patients with CD-positive tumors developed significantly more often both soft tissue recurrences and visceral metastases (P = .0007) and had a significantly shorter disease-free survival (P &lt; .0001). Eight-year overall survival of patients with high-level CD expression was 64% as compared with 90% in those with low-level expression (relative risk, 2.97; 95% confidence interval [Cl], 1.6 to 4.4; P &lt; .0001). According to a Cox multivariate model and a regression-tree analysis, high-level CD expression was an independent predictor of poor overall survival in conjunction with tumor size and S-phase fraction. CONCLUSION These results indicate that CD expression determined by immunohistochemistry is a powerful prognostic factor in ANN breast cancer. The most significant prognostic information was obtained when CD expression (predicting metastatic activity) was combined with estimate of cell-proliferation rate (S-phase fraction).
Pasteurization of milk proteins promotes allergic sensitization by enhancing uptake through Peyer’s patches
Authors: F. Roth‐Walter, M. C. Berin, P. Arnaboldi, C. R. Escalante, S. Dahan, J. Rauch, E. Jensen‐Jarolim, L. Mayer
Journal: Allergy (2008)

The underlying mechanisms responsible for allergic sensitization to food proteins remain elusive. To investigate the intrinsic properties (as well as the effect of pasteurization) of the milk proteins alpha-lactalbumin, beta-lactoglobulin and casein that promote the induction of milk allergy.Alteration of structure and immune-reactivity of native and pasteurized proteins was assessed by gel filtration and ELISA. Uptake of these proteins was compared in vitro and in vivo. The biological effect was assessed by orally sensitizing C3H/HeJ mice with milk proteins followed by a graded oral challenge. Required dose to induce anaphylaxis, symptoms and mean body temperature was recorded. Antigen-specific antibodies and cytokine production by splenocytes were analyzed.Soluble beta-lactoglobulin and alpha-lactalbumin but not insoluble casein were readily transcytosed through enterocytes in vitro and in vivo. Pasteurization caused aggregation of beta-lactoglobulin and alpha-lactalbumin inhibiting uptake by intestinal epithelial cells in vitro and in vivo. Furthermore, aggregation redirected uptake to Peyer's patches, which promoted significantly higher Th2-associated antibody and cytokine production in mice than their native counterparts. Despite this only the soluble forms of beta-lactoglobulin and alpha-lactalbumin elicited anaphylaxis (following priming) when allergens were administered orally. Aggregated beta-lactoglobulin and alpha-lactalbumin as well as casein required systemic administration to induce anaphylaxis.These results indicate that triggering of an anaphylactic response requires two phases (1) sensitization by aggregates through Peyer's patches and (2) efficient transfer of soluble protein across the epithelial barrier. As the majority of common food allergens tend to form aggregates, this may be of clinical importance.