tbuckley/cabot-search huggingface dataset:
Erlotinib given sequentially to capecitabine and vinorelbine as first-second line chemotherapy in metastatic breast cancer patients. A dose finding study
Authors: M. Venturini, T. Catzeddu, L. Del Mastro, C. Bighin, E. Maggi, M. Clavarezza, G. Lunardi, S. Pastorino, A. Lambiase, R. Rosso
Journal: Journal of Clinical Oncology (2004)

834 Background: The combination of capecitabine (C) and vinorelbine (V) is active and has an acceptable toxicity profile in metastatic breast cancer (MBC) patients(pts) pretreated with anthracyclines and taxanes. Overexpression of EGFR is present in a high percentage of breast tumors. Erlotinib (Tarceva) is an orally active inhibitor of EGFR tyrosine kinase. It is well tolerated and showed antitumor activity in several types of cancer overespressing EGFR. We report preliminary results of a dose finding study of Tarceva given sequentially to CV as 1°-2° line chemotherapy(CT) in MBC pts. Methods: MBC pts pretreated with anthracyclines and taxanes or with contraindications to these drugs are given V 25 mg/mq e.v.(day 1 and 8) and C 1000 mg/mq orally twice daily(days 1–14), every 3 weeks. After at least 6 cycles of CT(if stable disease) or 8 cycles(if complete/partial response) pts are treated with Tarceva at 3 dose levels(50–100–150 mg) continuously. Primary objective of this study is to determine the MTD, the DLT and the recommended dose of Tarceva given sequentially to fixed doses of CV. Three pts at each dose level are to be recruited and before escalating to the next level at least three pts should have received no less than 1 month of Tarceva monotherapy. Results: From February 2003 a total of 9 pts were enrolled. Median age: 55 (range 40–70). PS 0–1: 100% pts. A total of 8/9 pts(89%) had visceral metastases and the same number(89%) had 2 or more metastatic sites. All pts(100%) had received prior treatment with anthracyclines and 6 of them(67%) had also received prior taxanes. Response data after 3 CT cycles is available on 6 pts. Of these 3(50%) achieved PR, 2 (33%) had stable disease, 1(17%) had progression of disease.Until now 3 pts started Tarceva monotherapy at the first dose level(50 mg daily). All of them had received a total of 8 cycles of CT. Two pts reached one month of Tarceva therapy and no DLT was observed. A pharmacokinetic study was performed in one patient. Conclusion: The accrual of pts is ongoing and results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Von Willebrand’s Disease
Authors: Harvey R. Gralnick, Yvette Sultan, Barry S. Coller
Journal: New England Journal of Medicine (1977)

Studies of von Willebrand's disease typically show either a quantitative or a qualitative abnormality of the factor VIII/von Willebrand factor protein. In studies of five patients we found a combination of quantitative and qualitative defects. Quantitative abnormalities included decreased levels of procoagulant, antigen and von Willebrand factor activities in the plasma and in the column fractions of cryopercipitate from gel chromatography. Qualitative abnormalities included annormal migration or shape of the crossed antigen-antibody arcs, disproportionate reduction of von Willebrand factor in relation to antigen, altered gel elution patterns of procoagulant, and von Willebrand factor activities the negative carbohydrate stain of the VIII protein on polyacryl-amide-gel electrophoresis and, in two patients, a decreased sialic acid content of factor VIII protein. Our studies indicate that von Willebrand's disease comprises both quantitative and qualitative defects.
Immune Correlates of Intratumoral Il-12 Electroporation
Authors: R.H. Pierce, K.T. Takamura, S.A. Shirley, S.E. Chan, J. Lewis, J.S. Campbell, L. Fong, R. Heller, T.T. Diep, A.I. Daud
Journal: Annals of Oncology (2014)
The Effect of Estrogen Dose on Postmenopausal Bone Loss
Authors: Anthony Horsman, Mary Jones, Roger Francis, Christopher Nordin
Journal: New England Journal of Medicine (1983)

In order to establish whether the favorable effect of estrogen therapy on postmenopausal bone loss was dose related, we measured sequential changes in the cortical diameters of the metacarpals by radiographic morphometry in 120 normal postmenopausal women who were being treated with ethinyl estradiol in doses ranging from 5 to 50 micrograms daily. There was a net loss of bone at doses below 15 micrograms per day and a net gain at doses of 25 micrograms per day and above. At doses between 15 and 25 micrograms daily, bone was neither gained nor lost. The loss of bone with the low doses was due to expansion of the medullary cavity that was unaccompanied by any change in total bone width. There was no change in bone volume with the intermediate doses because endosteal resorption of bone was offset by periosteal apposition. The net gain of bone with the higher doses occurred because endosteal resorption was totally inhibited but periosteal bone apposition continued. Thus, in postmenopausal women the reduction in the rate of cortical bone loss in response to estrogen therapy depends on the dose administered.
Case 29-1999
Authors: Hardy Kornfeld, Eugene J. Mark
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 34-year-old woman was referred to a hospital in Texas because of an intermittent cough and hemoptysis.The patient had been well until nine months earlier, when her temperature rose to 39.4°C. Subsequently, she had a low-grade fever, which eventually resolved, and an intermittent cough. One month later, she consulted a physician after she had coughed up a small amount of blood while exercising. Physical examination was normal; no radiographs were obtained. She was given a cough preparation for “bronchitis.”Four days before she was referred to the hospi-tal, she returned to the physician because she had . . .
Racial/ethnic disparities in breast reconstruction after mastectomy
Authors: A. K. Alderman, S. T. Hawley, A. S. Hamilton, S. J. Katz
Journal: Journal of Clinical Oncology (2008)

6510 Background: There is concern that minority women have limited access to breast reconstruction despite federally mandated insurance coverage. Our purpose was to describe patterns of use, decision-making outcomes and barriers to breast reconstruction among Latinas. Methods: A sample of women age <79 years with early stage breast cancer was identified from the Surveillance, Epidemiology and End Results registry in Los Angeles. 1,338 eligible subjects completed a questionnaire at a mean of 9 months after diagnosis (response rate 71.3%). Chi-square and logistic regression were used for the analyses. Results: 493 (36.8%) of the respondents underwent a mastectomy. Receipt of breast reconstruction varied significantly by patient race/ethnicity: 35.9% whites, 28.4% blacks, 35.7% English-speaking Latinas, and only 13.2% of Spanish-speaking Latinas (p < 0.001). Compared to the other racial/ethnic groups, Spanish-speaking Latinas were least likely to be satisfied with their surgical decision and were most likely to face significant barriers to reconstruction. Comparing Spanish-speaking Latinas to whites, 42.2% vs. 9.0% had regret with their surgical decision (p<0.001); 19.3% vs. 42.9% had a preoperative plastic surgery consult (p=0.001); and 45.9% vs. 22.0% wanted more information about reconstruction (p<0.001). Conclusions: Large disparities exist in the use of breast reconstruction between Spanish-speaking Latinas and other racial/ethnic groups. Future efforts should be targeted at improving Spanish-speaking Latina's knowledge and access to reconstructive surgery. Use, outcomes and barriers to breast reconstruction after mastectomy Whites (N=122) Blacks (N=98) English- Speaking Latinas (N=112) Spanish-Speaking Latinas (N=139) P value * Recieved breast reconstruction 35.9% 28.4% 35.7% 13.2% <0.001 Satisfied with surgical decision 91.8% 89.9% 83.2% 65.7% <0.001 Regret with surgical decision 9.0% 12.0% 18.8% 42.2% <0.001 Reconstruction explained pre-operatively 75.4% 71.4% 70.5% 53.2% 0.0004 Consult with plastic surgeon pre-operatively 42.9% 35.3% 36.3% 19.3% 0.001 Wanted more information about reconstruction 22.0% 29.7% 30.6% 45.9% <0.001 * These disparities in the bivariate comparisons persisted after controlling for demographic and clinical factors No significant financial relationships to disclose.
Cystic Fibrosis of the Pancreas
Authors: Richard B. Goldbloom, Paul Sekelj
Journal: New England Journal of Medicine (1963)

THE development of special types of glass that are selectively permeable to specific ions has permitted the construction of glass electrodes capable of measuring the concentration of certain monovalent cations with a high degree of accuracy.The sodium electrode1 has previously been applied to the measurement of sodium-ion concentration in solutions and in biologic systems.2 3 4 5 We were interested in the possibility of measuring sodium activity at the skin surface without the induction of sweating, with the thought that such a method might be useful for the rapid diagnosis of cystic fibrosis of the pancreas. Accordingly, one of us (P.S.) suggested . . .
Influence of rituximab(R) -fludarabine(F) and R-bendamustine(B) therapy on the immune system in relapsed lymphoma
Authors: Kaori Ito, Masataka Okamoto, Maiko Ando, Yosuke Ando, Eri Suzuki, Akinao Okamoto, Yoko Inaguma, Takahiro Hayashi, Shigeki Yamada, Nobuhiko Emi
Journal: Annals of Oncology (2015)
β1 integrin mediated acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in non-small lung cancer cells.
Authors: Q. Deng, S. Zhou, B. Su, Y. Zhao, C. Zhou
Journal: Journal of Clinical Oncology (2010)

e13651 Background: With the general application of EGFR TKI in treatment for NSCLC, more and more adherent and acquired resistance to such agents happens. To further improve efficacy of this kind of agents, a better understanding of the mechanism of resistance is necessary. Methods: Gefitinib-resistant PC9/G cell lines was induced by exposure of PC9 cell lines to MNNG and gefitinib and maintained in the mediua containing 0.05 umol/L of gefitinib. The inhibitory effects of gefitinib and/or LY294002 and PD98059 on cellular proliferation were tested by MTT assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western Blot was used to detect expression of EGFR, phospho-EGFR, Akt and phospho-Akt. The different profiles of gene expression between PC9 and PC9/G cells were obtained by DNA microarray. β1 integrin was knocked down by transiently transfected siRNA. A scrambled sequence was used as control. The sensitivity to gefitinib of transfected cells was determined by MTT assay. Sequencing products were amplified by nested PCR. Apoptosis of transfected cells was assayed by TUNEL methods. Results: Resistant index of PC9/G to gefitinib was about 140 to 241 fold compared with PC9.Overexpression of β1 integrin was observed in PC9/G. Depletion of β1 integrin with shRNA results in inhibition of proliferation and promotion of apoptosis of PC9/G. Phosphorylation of Akt was less inhibited by gefitinib in PC9/G than in PC9. The restoration of sensitivity of PC9/G to gefitinib by LY294002, PI3-K inhibitor, and the diminished level of phospho-Akt induced by knock down of β1 integrin with RNAi. Conclusions: These findings suggest that β1 integrin signaling through PI3-K may be an important mechanism of resistance to EGFR TKIs and β1 integrin may be a therapeutic target for treatment of NSCLC unresponsive to EGFR inhibitors. No significant financial relationships to disclose.
Reperfusion for Right Ventricular Infarction
Authors: Louis J. Dell'Italia
Journal: New England Journal of Medicine (1998)

Hemodynamically important right ventricular myocardial infarction is an infrequent consequence of inferior myocardial infarction.1 The clinical triad of hypotension, clear lung fields, and elevated jugular venous pressure occurs in less than 10 percent of patients presenting with acute inferior myocardial infarction. However, the hemodynamic signs of right ventricular infarction can be induced by volume loading in an additional 20 percent of patients.2 Thus, there are considerably fewer cases of right ventricular dysfunction resulting from occlusion of the right coronary artery than there are cases of left ventricular dysfunction resulting from occlusion of the left coronary artery. Furthermore, right ventricular function . . .
Abstract 1598: Isolation and characterization of circulating melanoma cells by size filtration and fluorescent in situ hybridization
Authors: Masahiko Yanagita, Jason J. Luke, Cloud P. Paweletz, Elena Ivanova, Paul T. Kirschmeier, Stephen F. Hodi, Pasi A. Jänne
Journal: Cancer Research (2015)

Abstract Somatic mutations in BRAF are predictive of the clinical efficacy of BRAF and/or MEK inhibitors for advanced melanoma. Resistance to treatment is observed for most patients despite a high response rate to kinase inhibitors. While repeated tumor biopsy is the gold standard for evaluating genetic changes following treatment, this is not generally feasible. The analysis of circulating melanoma cells (CMCs) has the potential to be a non-invasive means of interrogating the biology underlying response and resistance. Here we report on the isolation, detection, and characterization of CMCs from patients using size filtration followed by immunoflourescence and/or fluorescent in situ hybridization (FISH) analyses. Blood from a cohort of 20 patients with advanced melanoma was collected in an initial proof of concept experiment. CMCs were identified in 14 out of 20 melanoma blood samples (70%) with a range of 2.5-99 CMCs per 3mL of blood by immunofluorescence (IF) using a cocktail of 4 melanoma specific antibodies (HMB45, MART-1, Tyrosinase and MiTF). Cells that appeared tumor like by microscopy, but that did not stain for CD45 or the cocktail of melanoma specific antibodies were also detected. To further characterize these cells, FISH was performed with a set of 4 melanoma-specific probes (RREB1, MYB, Centromere 6, CCND1). In a cohort of 13 patients with melanoma specimens that had paired blood specimens, CMCs were detected in all 13 specimens ranging from 7.2-76 CMCs per 3mL of blood with more identification by FISH in 10 out 13 samples. Additionally, cells that were double negative by IF were observed to be positive by FISH. CMCs are detectable in the majority of patients with advanced melanoma. Use of IF and FISH can help detect and characterize CMCs. These tools will be useful in characterizing treatment related changes in CMCs. Citation Format: Masahiko Yanagita, Jason J. Luke, Cloud P. Paweletz, Elena Ivanova, Paul T. Kirschmeier, Stephen F. Hodi, Pasi A. Jänne. Isolation and characterization of circulating melanoma cells by size filtration and fluorescent in situ hybridization. [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 1598. doi:10.1158/1538-7445.AM2015-1598
Case 30-2008
Authors: William J. Gradishar, Jennifer R. Bellon, Michele A. Gadd, Helen Anne D'Alessandro, Kristina Braaten
Journal: New England Journal of Medicine (2008)

A 47-year-old premenopausal woman came to this hospital for treatment of breast cancer. A mass that measured 5 cm in diameter was present in the left breast; needle biopsies showed infiltrating ductal carcinoma that was grade 2 of 3, hormone receptor–positive, HER2/neu-negative. An evaluation of the staging disclosed a solitary lesion in the T6 vertebral body, which was asymptomatic. A management decision was made.
Case 23-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, William S. Beck, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of Case First admission. A seventy-seven-year-old man was admitted to the hospital because of fatigue.He had been well until six months previously, when exertional dyspnea and ankle edema developed. Shortly thereafter cold sensitivity and a burning sensation in the legs occurred. Two months later there was the onset of fatigue and generalized weakness. Two weeks before entry he received an unknown antibiotic medication because of dental extractions.He had taken acetazolamide (Diamox) for several years because of glaucoma. He had had no weight loss, chills, fever, easy bruisability or exposure to toxins. There was no history of . . .
Signs of the times
Authors: S. L. Goh
Journal: BMJ (2010)

<b>1137</b> <b>Objectives</b>: Using PET with a specific and selective radioligand targeting nicotinic acetylcholine receptors (nAChR) would allow us to better understand various nAChR related CNS disorders. Most past efforts have been directed towards the development of nAChR agonists, and the use of radiolabeled nAChR agonists, such as 5-<sup>123</sup>I-A-85380, 2-<sup>18</sup>F-A-85380 and 6-<sup>18</sup>F-A-85380, have proven possible for in vivo imaging in humans. However, recent studies show that nAChR antagonists are effective in the treatment of smoking cessation. In addition, the use of radiolabeled nAChR antagonists would provide a much safer pharmacological profile avoiding most peripheral side effects that might be generated from radiolabeled nAChR agonists even at the tracer level; thus, PET imaging with nAChR antagonists would facilitate clinical application. <b>Methods</b>: Based on pharmacological tests, substitution at the 3’-pyridine position of a series of deschloroepibatidine analogues dramatically reduced agonist potency in all behavior measures as compared to epibatidine analogues. Among these analogues, N-methyl-3’-iodo epibatidine (NMI-EPB) displays high affinity towards α4β2 (Ki = 0.029 nM against [<sup>3</sup>H]epibatidine) and potent functional antagonist properties against nicotine-induced antinociception (AD<sub>50</sub> = 0.04 mg/kg in the tail-flick test). This combination makes it one of the most promising ligands for this development work. Here we report the C-11 radiolabeling of NMI-EPB and its evaluation in baboons with PET. <b>Results</b>: Our PET studies of [<sup>11</sup>C]NMI-EPB in baboon revealed its excellent ability to penetrate the blood-brain-barrier (~0.05% of inj. dose/cc, which was much higher than that obtained from 2- and 6-<sup>18</sup>F-A-85380 (&lt; 0.02%)) and localize selectively in the brain regions that are consistent with the known concentrations of nAChR. All of the radiolabeled plasma metabolites of [<sup>11</sup>C]NMI-EPB were polar species and are not expected to enter the brain. The reproducibility, specificity, saturability and reversibility of [<sup>11</sup>C]NMI-EPB were clearly shown via our characterization studies in baboon. Most importantly, our studies demonstrate that [<sup>11</sup>C]NMI-EPB exhibits relatively faster kinetics (t<sub>1/2</sub> = 60-90 min for clearance), and might possibly be able to achieve an equilibrium in vivo much faster than all existing radioligands. <b>Conclusions</b>: The high brain uptake, high signal to noise ratio and high specific binding of [<sup>11</sup>C]NMI-EPB strongly suggest a great potential to carry out imaging studies in humans. <b>Research Support (if any)</b>: Department of Energy(DE-AC02-98CH10886), Office of Biological Environmental Research and the National Institutes of Health (EB002630, DA-06278 and DA 12001).
Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management
Authors: Stephen M. Ansell
Journal: American Journal of Hematology (2016)

Disease overview : Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. Diagnosis: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups under the designation of classical HL. Risk stratification: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Risk‐Adapted Therapy: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. Am. J. Hematol. 91:435–442, 2016. © 2016 Wiley Periodicals, Inc.
Trigeminal Sensory Neuropathy
Authors: J. N. Blau, Malcolm Harris, Stanley Kennett
Journal: New England Journal of Medicine (1969)

Ten patients had varying degrees of sensory disturbance confined to the fifth cranial nerve. The second and third divisions were most commonly affected, but motor paresis and pain were notably absent, and the corneal reflex invariably retained. Five out of the 10 patients completely recovered over periods of a few weeks to months; in the remaining five, symptoms persisted to a variable extent. In one of the latter group trigeminal neuralgia developed. It is postulated that the condition parallels other transient cranial-nerve palsies — namely, those affecting the seventh and perhaps the sixth nerve —in which recovery frequently occurs.