tbuckley/cabot-search huggingface dataset:
Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malignancy.
Authors: J Vinholes, C Y Guo, O P Purohit, R Eastell, R E Coleman
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare the effects of two bisphosphonates on markers of bone resorption in a randomized double-blind trial for the treatment of hypercalcemia of malignancy. PATIENTS AND METHODS Thirty-two patients with a serum calcium (sCa) level &gt; or = 2.7 mmol/L that persisted after 48 hours of saline rehydration were randomized to receive pamidronate 90 mg or clodronate 1,500 mg. Bone resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp), deoxypyridinoline (Dpd), pyridinoline (Pyd), the cross-linking molecule at either the N-telopeptide (NTx) or the C-telopeptide (Crosslaps) regions of type I collagen, and free Dpd. RESULTS Both bisphosphonates restored normocalcemia, but the duration of action was longer after pamidronate (P &lt; .01). There was a mean pretreatment sevenfold increase in NTx, fivefold increase in Dpd and Crosslaps, and 2.5-fold increase in free Dpd. The changes in uCa were confounded by an increase in parathyroid hormone (PTH) (P &lt; .05), which, through effects on the kidney, inhibits calcium excretion. Most resorption markers showed a larger decrease after pamidronate than clodronate (P &lt; .01). NTx and Crosslaps showed the greatest decrease, being significantly different from any other marker in both arms (P &lt; .01). There was a significant correlation between Dpd, NTx, and Crosslaps (P &lt; .002), but not with uCa. CONCLUSION The superiority of pamidronate in controlling hypercalcemia is mirrored by the changes observed in these markers. uCa is not an accurate bone resorption marker, which reflects the renal handling of calcium by PTH. NTx and Crosslaps showed the largest increase at baseline and the greatest change after treatment, which suggests these new markers may be more sensitive indicators of bone resorption.
Inflammasome ASC-knock out attenuates the development of pulmonary hypertension caused by chronic alveolar hypoxia
Authors: Fadila Telarevic Cero, Karl Otto Larsen, Vigdis Hillestad, Ivar Sjaastad, Arne Yndestad, Pål Aukrust, Egil Lien, Else Marit Løberg, Geir Christensen, Ole Henning Skjønsberg
Journal: European Respiratory Journal (2014)

Background: Inflammasomes are molecular platforms which are part of the innate immunity and the best characterized is the NLRP3 inflammasome consisting of the receptor (NLRP3), the adaptor protein (ASC) and caspase-1, the effector cysteine protease which activate IL-18 and IL-1β. Increased levels of interleukin (IL)-18 have been found during experimental alveolar hypoxia (K.O. Larsen et al. Cardiovasc Res, 2008), which leads to pulmonary hypertension.  Objective: To study role of NLRP3 inflammasome in chronic hypoxia induced pulmonary hypertension.  Methods: Active caspase-1, IL-18 and IL-1β were measured by Western blot analysis of lung homogenates in WT, NLRP3-/- and ASC-/- mice exposed to 1 months of hypoxia in a tightly sealed chamber containing 10% oxygen. Right ventricular systolic pressure (RVSP) was measured with a microtipped transducer catheter after 3 months of hypoxia exposure.  Results: Chronic hypoxia induced increased protein levels of caspase-1, IL-18 and IL-1β in WT and NLRP3-/- mice. However, hypoxia-induced activation of the inflammasome was absent in ASC-/- mice shown by no increase of active caspase-1, IL-18 or IL-1β. RVSP of ASC-/- exposed to hypoxia was significantly lower than WT hypoxia (40.8±1.5 mmHg versus 55.8±2.4 mmHg, p‹0.001), demonstrating a lesser degree of pulmonary hypertension. RVSP of NLRP3-/- exposed to hypoxia was not significantly altered compared to WT hypoxia (52.4±2.3 mmHg versus 55.8±2.4 mmHg).  Conclusions: Altogether, our results show that ASC-/- mice are protected against hypoxia-induced pulmonary hypertension, suggesting inflammasome activation to be involved in the pathogenesis of the disease.
Stillbirth should be given greater priority on the global health agenda
Authors: Zeshan U Qureshi, Joseph Millum, Hannah Blencowe, Maureen Kelley, Edward Fottrell, Joy E Lawn, Anthony Costello, Tim Colbourn
Journal: BMJ (2015)

Stillbirths are largely excluded from international measures of mortality and morbidity.  Zeshan Qureshi and colleagues  argue that stillbirth should be higher on the global health agenda.
High expression of epithelial-mesenchymal transition (EMT) markers in malignant mesothelioma and possible therapeutic intervention using an N-cadherin antagonist
Authors: M. B. Suraokar, H. Lin, D. He, N. Llansa, G. Mendoza, D. Woods, L. Prudkin, J. J. Lee, I. I. Wistuba, A. S. Tsao
Journal: Journal of Clinical Oncology (2008)

8067 Background: Epithelial-mesenchymal transition (EMT) regulates metastatic progression and may have an integral role in the pathogenesis of malignant pleural mesothelioma (MPM), a disease characterized by 3 distinct histologic subtypes. Methods: We tested this hypothesis by conducting immunohistochemical (IHC) analysis of EMT-specific biomarkers in archival MPM tumors, correlated the biomarker levels to clinical outcome, verified the protein expression in MPM cell lines via Western blot analysis, and also performed IC50 assays on MPM cell lines using 3 novel N-cadherin antagonists (ADH-1, ADH-200024, ADH-200718). Results: A tissue microarray of 82 paraffin-embedded MPM tissues, which included 47 epitheliod, 26 biphasic, and 9 sarcomatoid subtypes, was used for the IHC analysis. MPM frequently expressed high levels of cytoplasmic and membrane β-catenin (64% of cases), membrane N-cadherin (47%), nuclear Snail (75%), and cytoplasmic vimentin (82%). In a small subset of tumors, cytoplasmic matrix metalloproteinase-9 (MMP-9, 12%) and integrin- α νβ6 (17%) showed high IHC expression. When analyzed as continuous variables, the amount of IHC expression did not correlate to patient demographics, overall nor progression-free survival. Epitheliod tumors had higher cytoplasmic vimentin than the non-epitheliod tumors (p=0.012) but no other statistically significant difference in biomarker expression. Western blot analysis confirmed the high expression of EMT biomarkers in mesothelioma cell lines e.g. Met5A, NC1-H28, MSTO-211H, NC1-H2052 and NC1-H2452. Loss of E-cadherin was seen in MSTO-211H with a corresponding increase in N-cadherin. Our preliminary cell viability assays on the above-mentioned mesothelioma cell lines showed IC50 value ranges for ADH-1 (1.3 mM - 9.7 mM), ADH-200024 (0.2 mM - 1.6 mM), and ADH-200718 (13 nM - 84 nM). Conclusion: EMT-specific biomarkers have high expression levels in MPM tumors and are a potential target for cancer therapy. ADH-200718 may have viable antitumor activity against MPM cell lines. No significant financial relationships to disclose.
Association Between Dna Repair Enzyme and Somatostatin Receptor in Glioblastoma Multiforme
Authors: M. Joonsalu, T. Jogi, M. Kase, A. Minajeva, J. Lukjanova, T. Metsaots, M. Vardja, T. Asser, J. Jaal
Journal: Annals of Oncology (2014)
Renal amyloidosis in a drug abuser.
Authors: A U Tan, A H Cohen, B S Levine
Journal: Journal of the American Society of Nephrology (1995)

Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.
Paraneoplastic pemphigus as the initial presentation of chronic lymphocytic leukemia
Authors:  van Mook WNK, M M Fickers, P H Theunissen, J A van der Kley, J A Duijvestijn, H H Pas, D C Flikweert
Journal: Annals of Oncology (2001)

The case history of a 61-year-old male patient is described, who presented with severe stomatitis, conjunctivitis and leukocytosis. The diagnosis chronic lymphocytic leukemia (CLL) stage A (0) was made, for which no treatment was necessary. Progression of stomatitis and conjunctivitis and erythosquamous skin lesions with bullae and vesiculae formation developed. Under the diagnosis of bullous pemphigoid the patient was treated with corticosteroids. The histologic and immunofluorescence examination of a skin biopsy was compatible with this diagnosis, and antibodies to skin could not be detected in a first serum sample. Pseudomonas was cultured from all lesions, the corticosteroids were stopped and antibiotic treatment was started, without clear effect. Because of progression of skin lesions and debilitation, the patient finally declined all treatment and died five weeks after admission. Post-mortem examination showed enlarged lymphnodes in the cervical, aortal en iliacal areas, with histology confirming the diagnosis of CLL. Indirect immunofluorescence with the second serum sample showed auto-antibodies in high titer directed against the intercellular epithelial substance. Immunoblot studies showed binding with the classic target antigens in paraneoplastic pemphigus. Re-examination of the histologic skin specimen and the result of direct immunofluorescence were in retrospect compatible with the diagnosis of paraneoplastic pemphigus.
VAT and fat
Authors: A. O'Rourke
Journal: BMJ (2000)

<h3>ABSTRACT</h3> It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes. Aging led to an increase in oxidation of protein thiols demonstrated by increased S-glutathionylation of cysteine residues on proteins from Old (24 months old at the start of the study) mouse hearts compared to Young (5-6 months old). This shift in the oxidation state of the proteome was almost completely reversed by 8-weeks of treatment with elamipretide. Many of the significant changes that occurred were in proteins involved in mitochondrial or cardiac function. We also found changes in the mouse heart phosphoproteome that were associated with age, some of which were partially restored with elamipretide treatment. Parallel reaction monitoring of a subset of phosphorylation sites revealed that the unmodified peptide reporting for Myot S231 increased with age, but not its phosphorylated form and that both phosphorylated and unphosphorylated forms of the peptide covering cMyBP-C S307 increased, but that elamipretide treatment did not affect these changes. These results suggest that changes to thiol redox state and phosphorylation status are two ways in which age may affect mouse heart function, which can be restored by treatment with elamipretide.
A phase II study of DJ-927 as second-line therapy in patients (pts) with advanced gastric cancer (GC) who have failed a 5-FU non taxane based regimen
Authors: T. Evans, R. Dobrila, R. Berardi, K. A. Sumpter, L. R. Wall, R. Oyama, D. A. Anthoney
Journal: Journal of Clinical Oncology (2006)

4081 Background: Most 1st-line combination chemotherapy regimens in pts with advanced GC include 5-FU. Taxanes are also active agents in GC, either alone or in combination. However, there is no recognized 2nd-line regimen for use in pts with advanced GC. DJ-927 is a semi-synthetic novel taxane with in vitro activity against GC cells lines. It is administered orally, with hematologic dose-limiting toxicity (DLT) in Phase I studies. The primary objective of this study was to determine the objective response rate of DJ-927 as 2nd-line therapy in pts with advanced GC. Methods: Eligible pts had confirmed advanced GC with no more than 1 prior systemic 5-FU-containing regimen for advanced disease, with adequate hematologic, renal and liver function, and with measurable disease. The starting dose in the 1st cohort of 6 pts was 27 mg/m 2 orally, every 3 weeks. If &lt; 2 DLTs occurred at this dose, the next cohort of 6 pts would start at a dose of 35 mg/m 2 , every 3 weeks, and all subsequent pts would be treated at the optimal dose level. Measurable disease was assessed after every 2 courses. Pharmacokinetic sampling was performed during course 1 only. Sample size based on a 3-outcome 1-stage design was calculated to be 27 pts evaluable for response, with ≥ 4 responses of 27 pts indicating that DJ-927 has activity in advanced GC. Results: 36 pts (male=25; female = 11), KPS ≥ 60%, with GC (n = 23) or OG junction cancer (n = 13), received 104 courses (median = 2; range 1–9) of DJ-927. 2 DLTs (febrile neutropenia; Grade 4 neutropenia &gt; 5 days) occurred at 35 mg/m 2 , and the optimal starting dose was confirmed as 27 mg/m 2 . 6 of 36 pts were not evaluable for response (&lt; 1 complete treatment course) due to early disease progression (3), toxicity (2), and drug not given (1). Response data is available for 26 of 30 evaluable pts with confirmed PR (n = 5), SD (15), and PD (6). Toxicity, ≥ grade 3, in evaluable pts (n = 33) included neutropenia (17), anemia (5), thrombocytopenia (4), diarrhoea (7), fatigue (5), lethargy (4), neutropenic sepsis (5). Conclusions: DJ-927 has modest activity in pts with GC who have failed a 5-FU non-taxane based regimen. Toxicities include neutropenia ± sepsis, diarrhoea and lethargy. Further studies of DJ-927 in combination with other active agents are warranted in pts with GC. [Table: see text]
The impact of PET-based staging on survival of patients with stage I lung cancer
Authors: M. Begum, L. Robinson, E. Sommers, G. Bepler
Journal: Journal of Clinical Oncology (2009)

7570 Background: Patients with completely resected stage I lung cancer have the best survival. Stage I, as defined by Mountain in 1997, includes tumors of any size located within one lobe of the lung without involvement of the parietal pleura, a distance of 2 cm or more from the carina, and no evidence for metastatic disease in any pulmonary, hilar, or mediastinal lymph node or distant site. The 5-year survival for such patients is 57–67% (Mountain, 1997). We hypothesized that the introduction of FDG-positron emission tomography (PET) scanning would lead to upstaging of stage I patients with a consequential increase in survival. Methods: To test this hypothesis, we compiled a database of all patients with stage I lung cancer that underwent a complete surgical resection at the Moffitt Cancer Center from 1996 to 2006. Results: During this 11-year period, 1230 patients fulfilled these criteria. Surgery was performed by two thoracic surgeons (LR and ES). Description of pts: 638 women, 592 men; 11 African-American, 1215 Caucasian; 18 Hispanic, 1202 Non-Hispanic; age range 28.1–94.0 y, mean 68.9 y, median 69.9 y; 26 pneumonectomies, 243 segmentectomies or wedge resections; 699 adeno-, 15 adenosquamous, 325 squamous, 25 large cell, 57 neuroendocrine carcinomas; maximum tumor diameter range 0.1–25 cm, mean 2.9 cm, median 2.3 cm; 477 dead (survival 0.0–138.8 months), 753 alive (survival 0.1–144.4 months). The median OS by year of resection was: 88.0 m (1996, N=49), 61.2 m (1997, N=52), 72.1 m (1998, N=73), 58.0 m (1999, N=87), 83.6 m (2000, N=100), 75.0 m (2001, N=114), 70.7 m (2002, N=133), &gt;55.7 m (2003, N=140), &gt;41.5 m (2004, N=158), &gt;33.1 m (2005, N=164), and &gt;17.9 m (2006, N=160). These differences were not statistically significant (log-rank p=0.72). PET scanning was initiated at the beginning of the year 2000. The median OS for the 261 patients treated between 1996 and 1999 was 70.7 m (95% CI: 53.9–84.0), and the median OS for the 969 patients treated between 2000 and 2006 was 75.1 m (95% CI: 66.4–83.7). This difference was not statistically significant (log-rank p=0.34). Conclusions: We conclude that the introduction of PET scanning has not impacted on the survival of patients with stage I lung cancer at our institution. No significant financial relationships to disclose.
Abstract 15547: Impact of Atrial Fibrillation on Healthcare Costs After Myocardial Infarction - A Community Cohort Study
Authors: Bijan J Borah, Veronique L Roger, Roger M Mills, Winslow Klaskala, Stephanie S Anderson, Alanna M Chamberlain
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) is frequent in myocardial infarction (MI), yet the incremental economic impact of AF, and the timing of its onset, on healthcare costs after MI is not known. Me...
Definitive chemoradiotherapy followed by salvage therapy for locoregional failure might be standard a treatment option for stages I-III esophageal squamous cell carcinoma
Authors: K. Muro, M. Najima, T. Hamaguchi, Y. Yamada, Y. Shimada, K. Shirao, Y. Ito, A. Imai, Y. Kagami, Y. Tachimori
Journal: Journal of Clinical Oncology (2005)

4069 Purpose: To evaluate the efficacy and toxicities of chemoradiotherapy (CRT) for clinical stages I-III (T1–3 N0–1 and M0) esophageal squamous cell carcinoma (ESCC). Methods: For stage I, treatment consisted of two 4-week courses of cisplatin (CDDP) 70 mg/m2 (day 1) and 5FU 700 mg/m2/day (days 1–4) combined with concurrent radiotherapy (RT) of 60 Gy in 30 fractions over 7 weeks with 1-week break. For stages II, III, consisted of two 5-week courses of CDDP 40 mg/m2 (day 1, 8) and 5FU 400 mg/m2/day (days 1–5, 8–12) combined with concurrent RT of 60 Gy in 30 fractions over 8 weeks with 2-week break, and for responders, two courses of chemotherapy were added. Results: From June 1997 to September 2003, consecutive 158 patients (pts) were retrospectively analyzed. Patient characteristics: age; median 63 (range 34–78), male/female; 132/26, PS 0/1/2; 84/70/4, stage I/IIA/IIB/III; 70/25/18/45, SCC/others with SCC component; 154/4. Of 70 pts with stage I, there were 64 complete responses (CRs) for CR rate of 91%. Regarding stage I, 6 residual cases could curatively undergo salvage therapy (ST) such as endoscopic mucosal resection or esophagectomy, and local recurrence or new lesion occurred in 11 (17%) of 64 CRs, who all succeeded in ST. Of 88 pts with stages II, III, there were 56 CRs for CR rate of 64%. Regarding stages II, III, 25 (45%) of 56 CRs showed recurrences, and 19 (76%) of 25 recurrences successfully underwent ST. Of 32 non-CRs, there were only 10 (31%) who underwent ST. Salvage surgery showed a longer overall survival compared to no surgical cases. With a median follow-up duration of 4.5 years, the 1, 3, 5-year survival rates of stage I were 96, 79, and 74%, respectively. With a median follow-up duration of 3 years, the 1, 2, 3-year survival rates for stages II, III were 77, 59, and 48%, respectively. These survival data are comparable with surgery in our hospital. Acute toxicities for CRT and late radiation morbidities increased dependent on the steps of stages, but those were acceptable. Conclusion: Definitive CRT for stages I-III ESCC achieves high CR rates, but ST for locoregional failure after CRT, which is frequent, is necessary to improve the longer prognosis. No significant financial relationships to disclose.
Effect of 4,4′-Oxydianiline on the Thyroid and Pituitary Glands of F344 Rats: A Morphologic Study With the Use of the Immunoperoxidase Method&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A S Murthy, A B Russfield, G J Snow
Journal: JNCI Journal of the National Cancer Institute (1985)

F344 rats of both sexes were fed one of three concentrations (0.02, 0.04, 0.05%) of 4,4'-oxydianiline (CAS: 101-80-4), an intermediate in the manufacture of polyimide resins, mixed in the diet for 2 years. The incidence of hepatocellular neoplasms was increased in all the 3 groups of male rats and in female rats of the middle- and high-dose groups. The incidence of hyperplastic and neoplastic changes in the follicular cells of the thyroid gland was increased in male and female rats of the middle- and high-dose groups. The population of thyrotrophs (thyrotropin-producing cells) was increased in the pituitary glands of rats with neoplasms of the thyroid gland. These cells were distinct from prolactin cells. The increase in the number of thyrotrophs suggested insufficient hormone production by the induced thyroid tumors.
Prospective Trial for clinical evaluation of TRACP 5b as serum marker of bone resorption and for monitoring an oral clodronat-medication in osteolytic metastases of breast carcinoma
Authors: A. Di Liberto, W. Schmidt, M. Friedrich
Journal: Journal of Clinical Oncology (2004)

862 Background:Tartrate-resistent acid phosphatase (TRACP 5b) has been described as marker enzyme of bone resorbing osteoclasts and can be recorded quantitatively. Throughout regular measurement during treatment with bisphosphonates the efficacy of this therapy can be controlled. The aim of this study was to test the clinical relevance of TRACP 5b-measurements within the scope of monitoring patients with osteolytic bone metastases of breast cancer Methods:18 patients with BC and osteolytic bone metastases have been included. All patients received an oral clodronate medication (1600 mg/d). TRACP 5b was measured as baseline value and every two weeks. TRACP 5b (standard value for postmenopausal women: 2,8 ± 0,7 U/l) was measured with an enzyme-immuno assay of medac Diagnostika (Wedel, Germany). Results:The baseline values of all patients showed a significant elevation of TRACP 5b (7,34 vs 2,8 U/l). There was a clear difference in the baseline values between patients (group 1) with > 3 regions of bone metastases and patients (group 2) with < 3 regions of bone metastases (10,34 vs 5,72 U/l). In the course of controls during therapy with clodronate both groups showed an continuous decrease of TRACP 5b levels. After more than 2 months of therapy in both groups there was a significant decrease of TRACP 5b levels compared with the TRACP 5b levels in the first two months (group 1: 3,91 vs 4,68 U/l; group 2: 12,39 vs 8,23 U/l). In patients with estimated progressive disease in radiologic controls we found no significant but a distinct re-increase of TRACP 5b levels whereas in patients with stable disease TRACP 5b levels decreased further on. Conclusions:The results demonstrate that TRACP 5b is a valid marker of bone resorption in osteolytic metastases of breast carcinoma. TRACP 5b levels correlate with the extent of bone metastases. To achieve a clear reduction of TRACP 5b levels a antiresorptive therapy over several weeks is necessary. Furthermore determination of TRACP 5b may indicate a progression or stable disease of bone metastases during therapy. No significant financial relationships to disclose.