tbuckley/cabot-search huggingface dataset:
Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy
Authors: N. Shinohara, T. Harabayashi, S. Suzuki, K. Nagao, S. Nagamori, H. Matsuyama, K. Naito, K. Nonomura
Journal: Journal of Clinical Oncology (2006)

4579 Background: The combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) has been shown to be effective in patients with advanced urothelial cancer. The aim of this presentation is to evaluate long-term followup outcomes in patients who had treated with standard cisplatin-based chemotherapy. Methods: The PIN regimen consisted of paclitaxel 175 mg/m 2 on day 1, ifosfamide 4.5 g/m 2 divided over days 1, 2 and 3, and nedaplatin 70 mg/m 2 on day 1; PIN was given every 28 days. The doses of nedaplatin and ifosfamide were reduced according to the impairment of renal function (24h CCr) just before starting each cycle of PIN therapy Results: Thirty two patients who had previously undergone cisplatin-based chemotherapy were entered onto the study (median age, 66 years; median performance status, 1, median 24h CCr, 62ml/min [29–119ml/min] ). Metastatic sites at study entry included the lymph nodes (24), lung (6), bone (5), primary (5), soft tissue (3), and liver (2). Among the 32 assessable patients, there were 5 CRs (16%) and 19 PRs (59%) for an overall RR of 75 % (95% confidence interval [CI], 59–91 %). The median time to progression was 8 months (range, 0–50+ months) and the median survival was 22 months (range, 4–52+ months). Twelve patients received the full dose of PIN combination (median 5 cycles) and 20 patients required dose reduction (median 3 cycles). Nine of 12 (75%) patients who were treated with the full-dose PIN combination obtained a CR or PR, as did 15 of 20 (75%) patients who required dose reduction. Grades 3 and 4 neutropenia occurred in all patients. Febrile neutropenia occurred in 8 (25%) patients. Grades 3 and 4 thrombocytopenia occurred in 8 (25%) patients. Grades 3 and 4 anemia was observed in 6 (19%) patients. Grade 3 neuropathy occurred in 1 (3%) patient, who could not continue to receive additional cycles of PIN combination after 3 cycles. No patient experienced renal failure. There were no treatment-related deaths. Conclusions: The PIN combination was highly active and tolerable in patients who had previously treated with cisplatin-based chemotherapy, and might be suitable for those with mild to moderate renal insufficiency. No significant financial relationships to disclose.
Tenascin is synthesized and secreted by rat mesangial cells in culture and is present in extracellular matrix in human glomerular diseases.
Authors: L D Truong, M W Majesky, J Pindur
Journal: Journal of the American Society of Nephrology (1994)

Tenascin (TN) is a large oligomeric protein recently described as a component of the extracellular matrix. The distribution of TN in adult kidney tissue has not been adequately evaluated, but preliminary data have suggested that TN is variably seen in rare mesangial areas and in stroma surrounding some tubules. The enlargement of the mesangial matrix (mesangial sclerosis) is a common feature of many renal diseases and is thought to be partially related to oversynthesis of the normal components of the mesangial matrix (collagen type IV, laminin, fibronectin, and heparan sulfate proteoglycans) by mesangial cells. However, the possibility that mesangial cells are also the source of other extracellular matrix proteins that participate in the process of mesangial sclerosis has not been explored. In this study, the synthesis of TN by cultured rat mesangial cells was documented by the following observations: (1) Northern hybridization of total RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2) immunoblotting of the protein extracted from the conditioned medium demonstrated four TN protein bands; (3) immunoblotting of the protein extracted from the mesangial cell lysate demonstrated at least four TN protein bands; and (4) immunohistochemical techniques identified TN within the cytoplasm of mesangial cells and in the surrounding extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
Early versus late referral to hospice care: A case-control study.
Authors: Michael Voisine, Saurabh Dahiya, Behdad Besharatian, Jennifer Friderici, James A. Stewart
Journal: Journal of Clinical Oncology (2014)

127 Background: Hospice care can improve quality of life (QOL) for patients with advanced cancer. Studies suggest that hospice services are offered late in the course of terminal illness; limiting patient comfort and QOL. Limited literature exists on barriers to timely hospice referral. We examined demographic and clinical characteristics associated with late hospice referral. We hypothesized that age, malignancy type, and performance status (PS) may predict late referral to hospice. Methods: Patients were age 18+ cared for by oncologists of Baystate Medical Practices, referred to Baystate Hospice from 1/1/08 to 12/31/2010. Demographics and diagnosis (e.g., breast, lung, GI) were abstracted from the electronic medical record. Referral interval was calculated as date of death minus date of referral. Late referrals (“cases”) were classified as interval quintiles 1 and 2; early referrals (“controls”) quintiles 4 and 5. Fisher’s exact test and Wilcoxon Rank Sum identified demographic and clinical characteristics associated with late referral. Multivariable logistic regression was used to identify independent predictors of late referral. Results: 209 patients met inclusion criteria. The median referral interval was 29 days (IQR 12, 57). In the multivariable model, ECOG score (OR 1.51 95% CI 1.09 2.08); dementia (OR 0.08, 95% CI 0.01, 0.82); CNS cancer (OR 0.14, 95% CI 0.03, 0.73); and unclassified cancer (OR 0.32, 95% CI 0.14, 0.73) independently predicted late referral. Age, race, and sex were not associated in uni- or multivariable comparisons. Conclusions: In this study of 209 patients with advanced cancer enrolled to hospice, malignancy type, dementia, and performance status are associated with late hospice referral. We believe it is important to track timing of referral and look for ways to reduce barriers.
Parathyroid hormone-related protein (PTHrp) expression in human bone metastases (BM)
Authors: L. Costa, A. Fernandes, A. G. Oliveira, K. Leitzel, S. Ali, J. Schaller, L. Demers, T. Guise, A. Lipton
Journal: Journal of Clinical Oncology (2004)

9696 Background: Substantial animal data support a major role for PTHrp in tumor induced osteolysis. However, the presence of PTHrp in BM in humans has not yet been established. The purpose of this study was to determine the presence and frequency of PTHrp expression in BM from different types of cancer. Methods: Bone pathologic fractures or BM biopsies from 64 patients, median age 63 (36–85), 36 female, were analysed. Thirty-two had breast carcinoma, 10-gastrointestinal, 6-lung, 6-prostate, and 10 several other types of cancer. The lesions were lytic in 48 patients, blastic in 10 and mixed in 6. Nineteen patients had pathologic fractures (PF). Formalin fixed, decalcified, paraffin embedded sections of metastatic lesions were stained by an immunohistochemical (IHC) method using a mouse monoclonal antibody (Chugai Pharmaceutical Co., Ltd.) to human PTHrp. The expression of PTHrp in cancer cells was graded according to the percentage of stained cells (0; 1: < 25%; 2: 25–75%; 3: > 75%) and the intensity of staining (1, 2 or 3). A final IHC score (0–9) was obtained for each patient. The Mann-Whitney test and the Kruskal-Wallis test were employed to analyse the correlation among clinical factors and the IHC score. Results: 56/64 (87.5%) of patients showed PTHrp expression in the cancer cells in bone. There was no statistically significant difference in PTHrp expression regarding the primary tumor site (breast versus non-breast; p= 0.22), the x-ray pattern of BM (lytic versus blastic, or mixed lesions, p=0.85), or ER/PR expression in breast cancer cells in bone (p= 0.35). There was a statistically significant difference in PTHrp expression in patients who had PF (median score= 6) compared to patients without PF (median score=2.5), p=0.0007. Conclusions: The expression of PTHrp in BM was high and independent of the primary tumor origin or the x-ray pattern of the bone lesions. PTHrp expression was significantly higher in patients who had PF. This study suggests that therapies targeting PTHrp to treat BM should be tried in different types of cancer and may be useful to prevent PF. No significant financial relationships to disclose.
Recombinant Resilin‐Based Bioelastomers for Regenerative Medicine Applications
Authors: Linqing Li, Atsushi Mahara, Zhixiang Tong, Eric A. Levenson, Christopher L. McGann, Xinqiao Jia, Tetsuji Yamaoka, Kristi L. Kiick
Journal: Advanced Healthcare Materials (2015)

The outstanding elasticity, excellent resilience at high‐frequency, and hydrophilic capacity of natural resilin have motivated investigations of recombinant resilin‐based biomaterials as a new class of bio‐elastomers in the engineering of mechanically active tissues. Accordingly, here the comprehensive characterization of modular resilin‐like polypeptide (RLP) hydrogels is presented and their suitability as a novel biomaterial for in vivo applications is introduced. Oscillatory rheology confirmed that a full suite of the RLPs can be rapidly cross‐linked upon addition of the tris(hydroxymethyl phosphine) cross‐linker, achieving similar in situ shear storage moduli (20 k ± 3.5 Pa) across various material compositions. Uniaxial stress relaxation tensile testing of hydrated RLP hydrogels under cyclic loading and unloading showed negligible stress reduction and hysteresis, superior reversible extensibility, and high resilience with Young's moduli of 30 ± 7.4 kPa. RLP hydrogels containing MMP‐sensitive domains are susceptible to enzymatic degradation by matrix metalloproteinase‐1 (MMP‐1). Cell culture studies revealed that RLP‐based hydrogels supported the attachment and spreading (2D) of human mesenchymal stem cells and did not activate cultured macrophages. Subcutaneous transplantation of RLP hydrogels in a rat model, which to our knowledge is the first such reported in vivo analysis of RLP‐based hydrogels, illustrated that these materials do not elicit a significant inflammatory response, suggesting their potential as materials for tissue engineering applications with targets of mechanically demanding tissues such as vocal fold and cardiovascular tissues.
Abstract 191: Functional Dissection of Myosin Binding Protein-C Phosphorylation
Authors: Manish K Gupta, James Gulick, Hanna Osinska, Jeanne James, Valerie Lasko, Michelle Nieman, John N Lorenz, Jeffrey Robbins
Journal: Circulation Research (2012)

Rationale: Phosphorylation of cardiac myosin binding protein C (cMyBP-C) plays an important role in cardiac function and is actively regulated both in the normal heart and during the development of cardiac disease. Hence it is critical to understand the mechanistic and functional consequences of cMyBP-C phosphorylation Objective: To examine the non-equivalency of the group of three phosphorylatable sites (Ser-273, Ser-282, and Ser-302) whose phosphorylation states have been defined as being essential when ablated in concert in a transgenic mouse model. However, the distinct role, if any, of each individual phosphorylation site is not established. Methods and Results: Three transgenic lines were generated: DAA that expressed cMyBP-C containing Asp273-Ala282-Ala302, AAD, in which a charged amino acid was placed at residue 302 (Ala273-Ala282-Asp302) and SDS Ala273-Asp 282-Ala302). The effects of these replacements were determined at the whole animal and organ levels. The DAA and AAD mice showed pathology that was more severe than either the cMyBP-C null animals or animals that expressed cMyBP-C that was unable to be phosphorylated at any of the three sites. Both the DAA and AAD hearts exhibited atrial enlargement, left ventricular chamber dilation, extensive interstitial fibrosis, irregular cardiac rhythm and sudden cardiac death. Ultrastructural studies of DAA mice confirmed myocyte disarray. Yeast two hybrid analyses were used to determine the effects of altering the charge at these sites with respect to the ability of cMyBP-C to bind to the S2 domain of myosin or cardiac actin. While phosphorylation at either Ser-273 or Ser302 did not affect myosin S2 interaction, substitution of Ser 282 with a charged residue prevented interaction of cMyBP-C with both S2 myosin and actin. Conclusion: Our results confirm the non-equivalency of these three sites in terms of the effects of their post-translational modifications on cMyBP-C functionality in the heart. Ser-282 appears to be the key residue in controlling S2 interaction with the protein. Chronic phosphorylation at one of these sites in the absence of the other, adjacent sites' ability to be phosphorylated leads to severe cardiac remodeling and sudden death.
Influence of &lt;italic&gt;p&lt;/italic&gt;-Hydroxypropiophenone on Liver Tumorigenesis in Rats Ingesting Ethionine and &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H SIDRANSKY, S CLARK, T BABA
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Influence of p-Hydroxypropiophenone on Liver Tumorigenesis in Rats Ingesting Ethionine and N-2-Fluorenylacetamide Get access Herschel Sidransky, Herschel Sidransky Search for other works by this author on: Oxford Academic PubMed Google Scholar Shirley Clark, Shirley Clark Search for other works by this author on: Oxford Academic PubMed Google Scholar Tsuneo Baba Tsuneo Baba Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 30, Issue 5, May 1963, Pages 999–1013, https://doi.org/10.1093/jnci/30.5.999 Published: 01 May 1963 Article history Received: 02 January 1963 Published: 01 May 1963
Screening for diabetes in general practice
Authors: B. Hagstrom
Journal: BMJ (2002)

Editor—Lawrence et al conclude in their paper that screening for diabetes in general practice by measuring fasting blood concentrations of glucose has a very low yield in patients whose sole risk factor for diabetes is age 45 or more.1 Our experience from opportunistic screening in a rural primary health centre in Sweden is different.

A sign in the waiting room during 1999 invited all visitors aged 40 or older at the centre in Storvik, a village of 6800 inhabitants, to have their blood concentrations of glucose tested. Altogether 249 patients accepted, of whom 72 had a non-fasting capillary blood concentration of glucose of >6.7 mmol/l.

The latter group was invited to return for two further tests. Sixty two showed up, and 18 of these had a capillary blood concentration of glucose of >6.1 mmol/l in both tests.2,3 Five were aged around 50, and eight were aged 75 or older. Altogether 349 tests were performed. The cost of materials and work per test was about £2.00.4

Thus we found 18 new diabetic patients at very low cost by opportunistic screening. Our screening method was simple: £40 to find a diabetic patient, or about £140 per person to find these five “younger” patients, is a low cost. To set the cut-off point for a normal random blood concentration of glucose to <6.7 mmol/l is said to give a sensitivity of 64% and a specificity of 92% in a well screened population.5

Since most people will visit a primary health centre once every five years, few cases are going to be missed. This is therefore an acceptable way of screening and does not entail any oral glucose tolerance tests. It is better to do something than nothing at all, and we offer all patients a blood glucose test at least once every five years from the age of 45. Patients with cardiovascular risk factors, such as hypertension and dyslipidaemia, are tested at regular visits at least yearly.
Effective control of chemotherapy-induced nausea and vomiting with oral prednisone and metoclopramide.
Authors: H J Senn, A Glaus, I Bachmann-Mettler
Journal: Journal of Clinical Oncology (1984)

Repeated oral doses of metoclopramide (50 mg) and prednisone (25 mg) completely prevented nausea and vomiting (N + V) in approximately 50% and substantially reduced N + V in an additional 27%-36% of 56 chemotherapy courses in 30 consecutive cancer patients who were receiving primarily cisplatin. Toxicity from this antiemetic regimen was minor. Simple oral N + V-prevention with metoclopramide and prednisone is as effective but less cumbersome and considerably less expensive than either high doses of intravenous corticosteroids and/or intravenous metoclopramide.
Rabies Virus CVS-N2c ΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability
Authors: Thomas R. Reardon, Andrew J. Murray, Gergely F. Turi, Christoph Wirblich, Katherine R. Croce, Matthias J. Schnell, Thomas M. Jessell, Attila Losonczy
Journal: Neuron (2016)
The first report on Campylobacter coli family outbreak detected in Poland in 2006
Authors: S Wardak, J Szych, M Sadkowska-Todys
Journal: Eurosurveillance (2008)

A family outbreak of gastroenteritis caused by Campylobacter coli occurred in May 2006 in Bielsko-Biala, in the south of Poland. Four members of a family had non-bloody diarrhea and abdominal cramps. C. coli were isolated in three of the four patients. PFGE and PCR-RFLP-flaA patterns confirmed the link between cases, showing the usefulness of these methods in outbreak investigation. At the same time, the epidemiological and environmental investigations of this outbreak were very limited and did not provide enough evidence to identify the source of infection, and thus to support the hypothesis formulated by the local epidemiologist. It is necessary to improve surveillance of campylobacteriosis mainly by multidisciplinary training of epidemiologists, microbiologists and general practitioners.
Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma.
Authors: R Haas, M Moos, A Karcher, R Möhle, B Witt, H Goldschmidt, S Frühauf, M Flentje, M Wannenmacher, W Hunstein
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma. PATIENTS AND METHODS Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count &gt; or = 20 x 10(9)/L and neutrophil count &gt; or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available. CONCLUSION Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
Evolution of chicken repeat 1 (CR1) elements: evidence for ancient subfamilies and multiple progenitors.
Authors: T L Vandergon, M Reitman
Journal: Molecular Biology and Evolution (1994)

Chicken repeat 1 (CR1) is an interspersed repetitive element that is a member of the non-long terminal repeat class of retrotransposons. A data set of chicken 95 CR1 elements was compiled and the phylogeny of the 52 elements with the most complete 3' ends was examined. We interpret the branching pattern as clustering into at least six subfamilies, designated A-F. The presence of highly similar elements within the B, C, D, and F subfamilies is evidence that a distinct progenitor has spawned each of these subfamilies. The nucleotide divergence between members of subfamily C was 5%-8%, suggesting that this subfamily has undergone a relatively recent burst of retrotransposition. The A and E subfamilies may have been spawned from ancestors of these four progenitors or from other, distinct progenitors. The consensus sequences for the six subfamilies showed considerable divergence, implying that the CR1 subfamilies are ancient. The CR1 elements in each subfamily have truncated 5' ends and a 3' end consisting of > or = 2 repeats of an 8-bp sequence. We estimate that there are approximately 100,000 CR1 elements in the chicken genome. Twelve CR1 sequences from avian species other than chicken were identified. Some of these sequences grouped into different subfamilies, demonstrating that multiple subfamilies existed early in avian evolution. Reptilian CR1 sequences were also identified, demonstrating that the CR1 element arose before the divergence of birds and reptiles.
Thrombasthenic mice generated by replacement of the integrin αIIb gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment
Authors: Diana Tronik-Le Roux, Valérie Roullot, Christel Poujol, Thierry Kortulewski, Paquita Nurden, Gérard Marguerie
Journal: Blood (2000)