tbuckley/cabot-search huggingface dataset:
Weight loss: An important but often overlooked clue for the diagnosis of cancer.
Authors: P. Peddi, S. Chitneni, M. Noel, K. A. Schwartz
Journal: Journal of Clinical Oncology (2010)

e19661 Background: One of the primary goals of care for cancer patients is to detect growth and or recurrence as early as possible. We retrospectively evaluated a weight change of 5% or more as an indicator of cancer growth or recurrence in 53 patients. In addition, we noted the frequency of physician recognition of the weight loss as well as the time delay in initiating appropriate diagnostic responses. Methods: Charts from 53 cancer patients with 5% or more weight loss on at least two occasions were reviewed. Patient's evaluations and outcomes derived at least in part from the clinical clue provided by the weight loss were also recorded. Results: The 53 patients were evaluated multiple times, average 2.9 visits per patient. Weight loss was not addressed on at least one or more occasions in 41 (74%) patients. Among the 41 patients 8 (19%) had new cancers with weight loss documented in the medical record, but overlooked by their primary care physician. Of the remaining patients 4 (9 %) had developed new metastasis, an additional 3 (7.5%) had progression of their primary disease and cancer recurrence was diagnosed in 1 (2.4%) patient. The reasons for the weight loss in the remaining 25 patients (61%) were due to side effects of chemotherapy, dysphagia, recent hospitalization, infection and unknown. In patients whose weight loss was not noted the time lag between the onset of weight loss and diagnosis of advancing cancer varied from 0.5 months to 15 months with a mean delay of 5.6 months. This compares with a mean delay of 1.1 months in those 12 patients whose evaluation was initiated as soon as their weight loss was documented in the chart (plt; 0.05). Conclusions: The importance of weight loss of as a clue to the diagnosis of a new cancer or to cancer progression is frequently not appreciated resulting in a significant delay in initiating diagnostic investigations. No significant financial relationships to disclose.
Iron Parameters and Relation To Prognosis In Elderly Patients With Aggressive Lymphoma Receiving First Line Immunochemotherapy: An Analysis Of The Lysa LNH 03-6B Study
Authors: Richard Delarue, Herve Tilly, Gilles Andre Salles, Catherine Thieblemont, Serge Bologna, Herve Ghesquieres, Olivier Hermine, Corinne Haioun, Andre Bosly
Journal: Blood (2013)
Abstract 17854: Relationship Between Tissue Prolapse After Percutaneous Coronary Intervention and Its Relation With Neointimal Hyperplasia at Follow-up by Serial Optical Coherence Tomography Examination
Authors: Tomoyo Sugiyama, Shigeki Kimura, Yosuke Yamakami, Keisuke Kojima, Yuichiro Sagawa, Hirofumi Ohtani, Keiichi Hishikari, Hiroyuki Hikita, Atsushi Takahashi, Mitsuaki Isobe
Journal: Circulation (2014)

Background: Tissue prolapse (TP) after stent implantation is sometimes observed on optical coherence tomography (OCT) after percutaneous coronary intervention (PCI). However, the clinical significance of TP on long-term outcomes has not been fully investigated. We sought to evaluate the relationship between TP just after PCI and neointimal hyperplasia (NIH) at the follow-up period by serial OCT examination. Methods: We evaluated 106 consecutive lesions in 106 patients (46 patients with acute coronary syndrome [ACS]; 60 patients with stable angina pectoris [SAP]) that underwent PCI with OCT examination. All lesions were treated with stent implantation (60 lesions with drug-eluting stents; 46 lesions with bare metal stents). Before PCI, plaque morphologies at the culprit sites on OCT were evaluated. TP after PCI was defined as tissue extrusion through the stent struts. TP area in each cross-sectional area (CSA) and TP volume defined as the sum of TP area in each CSA at 1-mm intervals throughout the stented ...
Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies
Authors: Sergio Gonzalez, Jade Berthelot, Jennifer Jiner, Claire Perrin-Tricaud, Ruani Fernando, Roman Chrast, Guy Lenaers, Nicolas Tricaud
Journal: Journal of Clinical Investigation (2017)

Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies.
Personalizing treatment in patients with castrate-resistant prostate cancer: A study of predictive factors for secondary endocrine therapies activity.
Authors: Yohann Loriot, Christophe Massard, Laurence Albiges, Mario Di Palma, Pierre Blanchard, Alberto Bossi, Anne Chauchereau, Bernard J. Escudier, Karim Fizazi
Journal: Journal of Clinical Oncology (2012)

213 Background: Several options have recently demonstrated activity, including survival improvement, in patients with prostate cancer progressing while on androgen deprivation therapy: chemotherapy (docetaxel, cabazitaxel), sipuleucel-T, and abiraterone. There is now an urgent need to identify predictive factors of efficacy for each of these treatments to assist decision-making in pts with castrate-resistant prostate cancer (CRPC). We attempted to identify predictive factors for activity of subsequent endocrine manipulations in patients with CRPC. Methods: Patients with CRPC included in the Institut Gustave Roussy clinical trials database who received endocrine manipulations (abiraterone, ketoconazole-hydrocortisone, DES, bicalutamide) for CRPC were reviewed. The predictive role on response and progression-free survival (PFS) of a series of clinical, biological, and radiological parameters was studied (Khi-2 test for response, Logrank test and Cox model for PFS). Results: 108 patients with CRPC who participated to 5 clinical trials were identified. The median duration of prostate cancer sensitivity to ADT (defined as the time from ADT initiation to the outset of castrate-resistance) was 16 months (range: 0–118 months). Timing of endocrine manipulation (before vs after docetaxel-based chemotherapy), presence of non-bone visceral metastases, the type of progression (clinical vs radiological), Performance Status, and PSA doubling time did not predict for response or PFS. In contrast, the previous duration of prostate cancer sensitivity to ADT (classified as ≥16 months and &lt;16 months) significantly and strongly predicted for both PSA response (58% vs 18%, p=0.01) and PFS (median PFS rates: 5 months (95%CI: 3.46–6.53) and 3 months (95%CI: 2.10–3.89) p&lt;0.043). Conclusions: A previous duration of prostate cancer sensitivity to ADT ≥16 months is the only significant predictive factor for efficacy of subsequent endocrine manipulations in patients with CRPC. This parameter shall be integrated into the decision-making process for these patients.
Destruction of Human Lymphoid Tissue-Culture Cell Lines by Human Peripheral Lymphocytes in 51Cr-Release Cellular Cytotoxicity Assays2
Authors: Eugene B. Rosenberg, James L. McCoy, Stanley S. Green, Francis C. Donnelly, David F. Siwarski, Paul H. Levine, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Destruction of Human Lymphoid Tissue-Culture Cell Lines by Human Peripheral Lymphocytes in 51Cr-Release Cellular Cytotoxicity Assays Get access Eugene B. Rosenberg, Eugene B. Rosenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar James L. McCoy, James L. McCoy Search for other works by this author on: Oxford Academic PubMed Google Scholar Stanley S. Green, Stanley S. Green Search for other works by this author on: Oxford Academic PubMed Google Scholar Francis C. Donnelly, Francis C. Donnelly Search for other works by this author on: Oxford Academic PubMed Google Scholar David F. Siwarski, David F. Siwarski Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul H. Levine, Paul H. Levine Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald B. Herberman Ronald B. Herberman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 345–352, https://doi.org/10.1093/jnci/52.2.345 Published: 01 February 1974 Article history Received: 08 June 1973 Accepted: 12 October 1973 Published: 01 February 1974
Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition
Authors: Leena A. Ibrahim, Lukas Mesik, Xu-ying Ji, Qi Fang, Hai-fu Li, Ya-tang Li, Brian Zingg, Li I. Zhang, Huizhong Whit Tao
Journal: Neuron (2016)
Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048
Authors: A. Klochikhin, R. Greil, E. Cohen, J. Vermorken, K. Harrington, M. Tahara, J.Y. Ge, J. Geib, F. Jin, B. Burtness
Journal: Annals of Oncology (2015)
Trends in chemotherapy for elderly patients with non-small cell lung cancer: The experience of one institution
Authors: Y. Kim, Y. Nishiwaki, K. Yoh, S. Niho, K. Goto, H. Ohmatsu, K. Kubota, N. Saijo
Journal: Journal of Clinical Oncology (2009)

e19081 Background: In approximately the year 2000, the results of a number of important studies of non-small-cell lung cancer (NSCLC) were published. These included the first elderly-specific phase III trial and phase III trials showing a survival benefit for docetaxel when used as second-line chemotherapy. These results had a significant impact on clinical practice relating to advanced NSCLC in elderly patients. Methods: Between July 1992 and December 2003, 223 patients with NSCLC aged ≥70 years received chemotherapy alone as their initial treatment at the National Cancer Center Hospital East. These patients were divided into 2 groups: those that began treatment between 1992 and 1999 (group A) and between 2000 and 2003 (group B). The details of chemotherapy regimens and outcomes were compared. Results: In group A, 83% of patients received platinum-based chemotherapy, two-thirds of these regimens comprised platinum[[Unsupported Character - ]]plus second-generation combination chemotherapy. In contrast, although 55% of patients received platinum-based chemotherapy in group B, 41% of patients received non-platinum-based chemotherapy. Among patients in group B, performance status was significantly associated with the selection of platinum-based or non- platinum-based chemotherapy; age was marginally associated with this selection. In group A, second-line chemotherapy was administered to only 4 patients (5%) and no patients received third-line chemotherapy. In group B, second-line and third-line chemotherapy was administered to 62 (42%) and 22 (15%) patients, respectively. Median survival time (MST), 1-year survival rate, and 2 year-survival rate were 6.7 months, 14%, and 7%, respectively, in group A, and 8.1 months, 35%, and 20% in group B (p = 0.0109). However, these differences disappeared when patients treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) were removed from the analysis (6.7 months in group A vs. 6.9 months in group B, p = 0.3684). Conclusions: In and after the year 2000, chemotherapy regimens changed greatly and survival of elderly patients significantly improved. However, the improvement in survival seems to be due mostly to the use of EGFR-TKI treatment. No significant financial relationships to disclose.
Hypertension and Obesity
Authors: Louis Tobian
Journal: New England Journal of Medicine (1978)

IN our recently heightened zeal to treat hypertensive patients with pressure-lowering drugs, we may be overlooking another potent avenue of therapy. The article by Reisin et al. in this issue of the Journal points this paradox out in very clear terms. They advised 81 obese hypertensive patients to eat fewer calories while on an ordinary balanced diet with generous helpings of salty low-calorie foods. These patients lost about 9.5 kg in weight after more than two months on the low-calorie diet. This weight reduction was accompanied by highly significant falls in blood pressure, an average drop of 26 mm Hg . . .
A phase I study of BAY 43–9006, a dual inhibitor of Raf and VEGFR kinases, in Japanese patients with solid cancers
Authors: H. Minami, K. Kawada, H. Ebi, K. Kitagawa, Y.-I. Kim, K. Araki, H. Mukai, M. Tahara, H. Nakajima, K. Nakajima
Journal: Journal of Clinical Oncology (2005)

3062 Background BAY 43–9006 is a novel inhibitor of Raf kinase and vascular endothelial growth factor (VEGF) tyrosine kinases. BAY 43–9006 has shown in vivo antitumor activity against various cancers by inhibiting tumor cell proliferation and angiogenesis. We have conducted a phase I study of BAY 43–9006 in Japanese cancer patients to decide a recommended dose and to clarify profiles of toxicities and pharmacokinetics. Methods Patients with solid tumors refractory to standard therapy, adequate organ functions, performance status of 0 or 1, and a life expectancy of ≥ 12 weeks were enrolled. Successive cohorts of patients received a single oral dose of 100 to 600 mg followed by a 7-day observation period and then received the same dose bid without interruption. Results Thirty-one patients including 10 non-small cell lung (NSCLC) and 3 renal cell cancer patients were treated. Three, 15, 6 and 7 patients were treated at 100, 200, 400 and 600 mg bid, respectively. Common drug-related adverse events were skin toxicities, laboratory data abnormalities, diarrhea and anorexia. At 200 mg bid, one patient developed grade 3 diarrhea and another two had grade 4 transient elevations of pancreatic enzymes. Grade 3/4 asymptomatic and transient elevations of pancreatic enzymes were observed in 2/3 patients at 400 and 600 mg bid, respectively. DLT definition was modified to consider not only NCI-CTC grading but also clinical significance. At 600 mg bid, dose-limiting grade 3 fatigue was observed in one patient and 5 patients experienced grade 2 hand-foot syndrome that were more painful and severe than those at 400 mg bid. The AUC and Cmax of BAY 43–9006 linearly increased with dose. At 400 mg bid, plasma trough concentrations (1.22 - 14.77 mg/L) exceeded the IC50 (1.2 mg/L) of BAY 43–9006 shown to inhibit tumor cell proliferation. Partial responses by RECIST were observed in a NSCLC patient (200 mg bid) and a renal cell cancer patient (600 mg bid). Two other NSCLC patients treated at 200 or 400 mg bid had stable disease ≥ 24 weeks. Conclusions BAY 43–9006 at 400 mg bid is recommended for phase II studies based on safety and efficacy data. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Yakuhin, Ltd. Bayer Yakuhin, Ltd.
Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy
Authors: Miriam F. Gasia, Subrata Ghosh, Remo Panaccione, Jose G. Ferraz, Gilaad G. Kaplan, Yvette Leung, Kerri L. Novak, Cynthia H. Seow, Marietta Iacucci
Journal: Clinical Gastroenterology and Hepatology (2016)
Computational prediction of formulation strategies for beyond-rule-of-5 compounds
Authors: Christel A.S. Bergström, William N. Charman, Christopher J.H. Porter
Journal: Advanced Drug Delivery Reviews (2016)

The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity. These physicochemical properties move the compounds towards beyond rule-of-5 (B-r-o-5) chemical space and often result in lower water solubility. For such B-r-o-5 compounds non-traditional delivery strategies (i.e. those other than conventional tablet and capsule formulations) typically are required to achieve adequate exposure after oral administration. In this review, we present the current status of computational tools for prediction of intestinal drug absorption, models for prediction of the most suitable formulation strategies for B-r-o-5 compounds and models to obtain an enhanced understanding of the interplay between drug, formulation and physiological environment. In silico models are able to identify the likely molecular basis for low solubility in physiologically relevant fluids such as gastric and intestinal fluids. With this baseline information, a formulation scientist can, at an early stage, evaluate different orally administered, enabling formulation strategies. Recent computational models have emerged that predict glass-forming ability and crystallisation tendency and therefore the potential utility of amorphous solid dispersion formulations. Further, computational models of loading capacity in lipids, and therefore the potential for formulation as a lipid-based formulation, are now available. Whilst such tools are useful for rapid identification of suitable formulation strategies, they do not reveal drug localisation and molecular interaction patterns between drug and excipients. For the latter, Molecular Dynamics simulations provide an insight into the interplay between drug, formulation and intestinal fluid. These different computational approaches are reviewed. Additionally, we analyse the molecular requirements of different targets, since these can provide an early signal that enabling formulation strategies will be required. Based on the analysis we conclude that computational biopharmaceutical profiling can be used to identify where non-conventional gateways, such as prediction of 'formulate-ability' during lead optimisation and early development stages, are important and may ultimately increase the number of orally tractable contemporary targets.
Global genetic pattern analysis using cDNA microarray-based CGH for prognosis prediction to FAC neoadjuvant and adjuvant chemotherapy in locally advanced breast cancer patients
Authors: S. Y. Rha, M. Y. Seo, H. Jeung, G. Lee, S. Yang, W. I. Yang, G. E. Kim, B. S. Kim, H. Chung
Journal: Journal of Clinical Oncology (2004)

9544 Background: In locally advanced breast cancer, selection of adjuvant regimen after neoadjuvant chemotherapy and surgery is still in controversy. Methods: 46 locally advanced breast cancer patients were treated with FAC (5-fluorouracil, adriamycin, cyclophosphamide) both in neoadjuvant and adjuvant chemotherapy. We evaluated the clinical and pathologic responses, and prognosis. Genomic DNA extracted from the paraffin embedded tissues of 12 core biopsy, 46 surgically resected and 4 relapsed tissues were used for cDNA microarray-based CGH using 17K human cDNA gene chip. To identify drug-resistance related genes, we compared the genetic changes between 12 paired specimens taken before and after neoadjuvant chemotherapy in the same patient. 46 cases from surgically resected tissues were assessed to identify the prognosis signatures. Results: Median age of the patients was 45 (range 32–70), and 39 patients (85%) showed pathological response after neoadjuvant chemotherapy. Five-year disease-free and overall survival rates were 33% and 52%, respectively. Significant prognostic factors after the surgery were nodal state and stage. Differential patterns of gene copy number changes between before and after neoadjuvant treatment were observed, and 333 genes of differentially changed genes correlated with treatment resistance. 585 genes were distinctively changed in relapsed patients compared to disease-free patients, and most of 102 selected genes located on 1, 3p, 8q and 17q, suggesting the FAC-resistance related area. Two-way hierarchical clustering with selected genes correlated with disease recurrence (p< 0.01). With 1336 genes that had significant difference between recurred and non-recurred group, 21 of 30 recurred cases were correctly classified as the recurred group with the error rate of 30% based on the cross-validation with PAM. Conclusions: We demonstrate the potential of array-CGH based global genetic patterns associated with FAC resistance, thus permitting guideline for the selection of adjuvant regimen after surgery with neoadjuvant chemotherapy. No significant financial relationships to disclose.
Enhancer of zeste homologue 2 ( EZH-2) expression in breast cancer: a novel marker and potential target
Authors: S. Bandyopadhyay, Z. Nahleh, R. Ali Fehmi, H. Arabi, W. Sakr, A. Munkarah, M. Kruger
Journal: Journal of Clinical Oncology (2009)

e22154 Background: EZH-2 is a protein involved in cell cycle regulation; it belongs to the Polycomb group of proteins and has been suggested to be associated with aggressive breast cancer. In hormone receptor negative (HR-) breast carcinomas, novel therapeutic targets are needed. Few markers have achieved the success of Her-2/neu as targeted therapy making the search for novel treatment strategies imperative. In our study we investigate the expression of EZH2 in a cohort of hormone receptor negative breast carcinomas. Methods: We identified a consecutive cohort of 84 cases of HR- breast carcinoma in 2005–2006, from the Pathology department archives. Tumor grade, size, presence or absence of DCIS, lymph node status and Her2/neu expression were documented. The race of the patients was also noted. Immunohistochemical staining for EZH2 was performed on paraffin embedded sections. Nuclear expression of EZH2 was considered as positive and the percentage of cells staining positive was estimated. Using the Mann-Whitney U test, the expression of EZH2 was correlated with the tumor characteristics listed above. Results: The mean expression of EZH2 in HR- tumors was estimated at 74% with a median of 80% (0–90). Most of these cases (n= 61) were triple negative; 23 cases were HER-2/neu positive by established criteria. Increasing expression of EZH2 was correlated with increase in tumor size (&gt;2 cm) and increased incidence of lymph node metastasis. No correlation was seen with tumor grade, the presence or absence of DCIS and Her2/neu expression. Race did not appear to have an impact on EZH2 expression. Conclusions: Our findings suggest that EZH2 is expressed in the majority of HR - breast cancer and is associated with aggressive breast carcinomas. EZH2 could be an important therapeutic target in this patient population. The study is ongoing to further characterize EZH2‘s role and its association with survival. No significant financial relationships to disclose.