tbuckley/cabot-search huggingface dataset:
Abstract 5494: ADAMTS-7 is Critical for Vascular Smooth Muscle Cell Migration and Neointima Formation in Injured Rat Carotid Artery
Authors: Wei Kong, Li Wang, Xue Bai, Bo Liu, Yi Zhu, Xian Wang
Journal: Circulation (2008)

Migration of vascular smooth muscle cells (VSMCs) plays an essential role during vascular development, in response to vascular injury and during atherogenesis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases during VSMCs migration. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), a recently described family of proteinases, is capable of degrading vascular ECM proteins. However, the relevance of ADAMTS family members in cardiovascular disease is poorly understood. In this study, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. Denudation of rat carotid arteries with a balloon catheter led to an initial decrease of ADAMTS-7 protein level in injured compared with sham-operated arteries within the first 24 hours, followed by a subsequent increase during the 4 to 14 days after injury. In primary VSMCs, the pro-inflammatory cytokine TNF-α increased ADAMTS-7 mRNA level through transcriptional factors nuclear factor-kappa B and AP-1. VSMCs infected with ADAMTS-7 adenovirus (Ad-ADAMTS-7) greatly accelerated their migration and invasion in vitro . Conversely, suppression of ADAMTS-7 expression by small interfering RNA (siRNA) markedly retarded VSMC movement by 50% than that with scramble siRNA. At 7 days after injury, the neointimal area of the vascular wall was sixfold greater in Ad-ADAMTS-7-infected than that in Ad-GFP-infected vessels (3.10±0.88 vs. 0.52±0.28 ×10 4 μm 2 , n=8 per group, P &lt;0.05). By contrast, perivascular administration of ADAMTS-7 siRNA, but not scramble siRNA to injured arteries resulted in prolonged ADAMTS-7 silencing and diminished neointimal thickening without affecting medial areas. This inhibitory effect was sustained up to 14 days after injury. As well, ADAMTS-7 mediated degradation of the vascular ECM cartilage oligomeric matrix protein (COMP) in injured vessels, which might facilitate VSMC migration and neointimal thickening. ADAMTS-7 directs VSMC migration and neointima formation and therefore may serve as a novel therapeutic target for vascular restenosis and atherogenesis.
Endoscopic treatment of fistula after sleeve gastrectomy: results of a multicenter retrospective study
Authors: Dimitri Christophorou, Jean-Christophe Valats, Natalie Funakoshi, Claire Duflos, Marie-Chistine Picot, Bruno Vedrenne, Frédéric Prat, Phillipe Bulois, Julien Branche, Sébastien Decoster, Emmanuel Coron, Antoine Charachon, Guillaume Pineton De Chambrun, David Nocca, Paul Bauret, Pierre Blanc
Journal: Endoscopy (2015)

Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment.This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis.A total of 110 patients were included, of whom 6 (5.5 %) healed spontaneously, 81 (73.6 %) healed following endoscopic treatment, and 19 (17.3 %) healed following surgery. Healing rates following endoscopic treatment were 84.4 % in the first 6 months of treatment (65/77), 52.4 % for treatment lasting 6 - 12 months (11/21), and 41.7 % after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6 %). A total of 177 esogastric stents were placed in 88 patients (80.0 %). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval < 21 days between fistula diagnosis and first endoscopy (P = 0.003), small fistula (P = 0.01), interval between LSG and fistula ≤ 3 days (P = 0.01), no history of gastric banding (P = 0.04).Endoscopic treatment facilitated healing of post-LSG fistula in 74 % of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered.
Abstract 18848: Frequent Missed Opportunities to Avert Heart Failure Hospitalization
Authors: Brian G Howard, Lynne W Stevenson, Akshay Desai
Journal: Circulation (2012)

Background: Although emphasis has been placed on events after discharge for patients with heart failure (HF), reducing hospitalization may also require focus on the route prior to hospitalization. We mapped the timing of worsening symptoms and provider contacts in the weeks leading up to HF hospitalization. Methods: Scripted interviews were conducted in 100 patients admitted with HF to assess when they recognized worsening symptoms, contacted their provider, and made any medication changes. Results: Patients recognized worsening s ymptoms including increased fatigue, lower extremity swelling, and worsening dyspnea on exertion a median of 17.5 days before hospitalization; this prompted contact with a medical provider prior to ED presentation in 74 patients. Initial provider contact occurred a median of 14 days prior to hospitalization and led to medication changes in 48 patients. 52 patients had multiple contacts with ambulatory providers prior to being hospitalized. Conclusions: Patients hospitalized for HF often contact a physician prior to hospital admission. Many receive pre-hospital interventions, though in our sample, these were insufficient to avert eventual admission. These data demonstrate the potential opportunity to decrease HF admissions by providing more effective intervention and rapid re-evaluation after patients call with worsening symptoms.
Pharmacokinetic and Pharmacodynamic Properties of a Biosimilar Rituximab (Reditux®) Are Identical to the Innovator Brand MabThera®– Experience from a Tertiary Cancer Centre in Western India
Authors: Hari Menon, Akanksha Yadav, P.G Subramanian, Manju Sengar, Sanhita Rath, Krunal Kavathiya, Vikram Gota
Journal: Blood (2014)
Clinical relevance of the detection of tumor cells in the bone marrow of patients before lung cancer surgery.
Authors: R. Nakahara, M. Anraku, A. Ui, N. Oohata, H. Matsuguma, S. Igarashi, K. Yokoi
Journal: Journal of Clinical Oncology (2010)

10603 Background: To investigate the correlation between the presence of tumor cells in the bone marrow aspirate of patients before lung cancer surgery and clinicopathological variables, recurrence, and prognosis. Methods: Of patients who had undergone surgery for lung cancer in our hospital between May 2001 and March 2003, 103 who had given consent for bone marrow aspiration were studied. On the day of surgery, bone marrow was aspirated under general anesthesia. Nucleated cells were isolated, smeared on glass slides, and immunohistochemically stained with monoclonal antibody AE1/AE3 to detect epithelial cells. Tumor cells were identified by a pathologist. The correlation between the presence or absence of these marrow tumor cells and clinicopathological variables, recurrence, and prognosis was examined. Results: The follow-up period was 1-100 months, with a mean of 67 months. Tumor cells were detected in the bone marrow of 29 (28%) of the 103 patients. p T3-4, St 3-4 tumors were more significantly associated with the appearance of tumor cells in the bone marrow, compared to p T1-2, St 1-2 tumors. Vascular invasion- and node-positive tumors tended to be associated with the appearance of marrow tumor cells. The 5-year survival rate of cancer-death patients tended to be lower in the tumor cell-positive than in the tumor cell-negative group (74 vs. 87%, respectively, p = 0.0751). Twelve (41%) of 29 patients in the tumor cell-positive group developed recurrence, and the 5-year recurrence-free survival rate was significantly lower (that is, the recurrence rate was significantly higher) in the tumor cell-positive than in the tumor cell-negative group (56 vs. 80%, respectively, p = 0.0130). Extrathoracic distant metastasis was observed in 7 (58%) of the 12 recurrent patients in the tumor cell-positive group, which was slightly higher than the 36% for the tumor cell-negative group. Conclusions: Patients with marrow tumor cells before surgery tended to more frequently develop distant metastasis and recurrence, and are therefore well indicated for postoperative adjuvant systemic therapy. No significant financial relationships to disclose.
Arterial bicarbonate as a determinant of the length of non-invasive ventilation (NIV) in COPD patients with acute hypercapnic respiratory failure (AHRF)
Authors: Sushil Agarwal, Vikas Punamiya, Shiva Bikmalla, Christopher Bond, Biman Chakraborty, Harjeevan Gill, Ben Beauchamp, Rahul Mukherjee
Journal: European Respiratory Journal (2012)

Introduction:  Factors related to length of stay are complex and related to many non-medical factors, however length (duration) of NIV treatment is not. Although the associations of mortality of patients requiring NIV are well-documented (Thomas A  et al .  Thorax  2010 ;  65 :4. A33.), the determinants of the length of NIV have not been clearly elucidated, which we decided to investigate.   Methods : A retrospective analysis of the initial arterial blood gas bicarbonate (HCO 3 mmol/L)values on 115 consecutive episodes of NIV for at a dedicated respiratory NIV unit from 01 Jan to 31 Oct 2011 was carried out. Analysis of blood gases and duration of use of NIV (in days) was documented and analyzed.   Results : There were 115 patients admitted with AHRF with COPD. Plotting a graph with HCO 3  and length of NIV we see that it has a linear relationship.  The p-value for HCO 3  as a determinant of length of NIV is 0.00084, which suggests that it is significant.   Conclusion:  This scientific survey indicates that the length of NIV therapy in patients in AHRF increases with a higher HCO 3 . Though outcome and mortality is closely linked to the pH, length of NIV is more closely linked to the HCO 3 . This is explained by the fact that people with higher HCO 3  are likely to have had chronic respiratory failure for longer and are likely to take longer to recover from the respiratory failure.
Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.
Authors: J J Lokich, R A Kane, D A Harrison, W V McDermott
Journal: Journal of Clinical Oncology (1987)

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.
Modification of Pancreatic Carcinogenesis in the Hamster Model. XII. Dose-Related Effect of Ethanol<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: P M Pour, H A Reber, K Stepan
Journal: JNCI Journal of the National Cancer Institute (1983)

Ethanol (E) was given to outbred Syrian golden hamsters in drinking water at a 5% (wtjvol) concentration for life beginning either before or after a single dose of N-nitrosobis(2-oxopropyl)amine (BOP). No effects on tumor induction were seen in the pancreas or in other BOP target tissues (e.g., the common duct and gallbladder), whether E was given immediately after or 4 weeks before and immediately after BOP. These results sharply conflicted with our previous findings in which a higher concentration of E (25% wt/vol) inhibited BOP-induced pancreatic lesions, and they indicated a dose-related action of E on pancreatic carcinogenesis. Development of a few acinar cell foci in hamsters treated with BOP and E, but not in those treated with E alone or BOP alone, indicated that E in this concentration alters pancreatic functions without rnodifyinq carcinogenesis.
Integrated development of s-<i>trans, trans</i>-farnesylthiosalicyclic acid (FTS, salirasib) in advanced pancreatic cancer
Authors: D. Laheru, M. Rudek, G. Taylor, H. Goldsweig, N. V. Rajeshkumar, S. Linden, M. Angenendt, D. Le, R. Donehower, A. Jimeno, M. Hidalgo
Journal: Journal of Clinical Oncology (2009)

4529 Background: The Ras signaling pathway stands as a strategic target in pancreatic cancer. S-trans,trans-farnesylthiosalicyclic acid (FTS) inhibits Ras dependent cell growth by dislodging all of the isoforms of Ras from membrane binding sites. Here we studied the activity of this agent in patients with advanced pancreatic cancer. Methods: Patients with treatment naïve advanced peri-ampullary cancer were treated with gemcitabine (Gem) administered at standard dose and schedule + FTS administered orally at doses of 200–800 mg bid 21 days of a 28 day cycle. Patients were treated until progression or protocol defined DLT. Plasma samples were collected when FTS was administered alone (C1D7 or C1D22) and in combination (C1D15 or C1D8) to characterize FTS pharmacokinetics. Plasma samples were collected when Gem was administered alone (C1D1) and in combination (C1D15 or C1D8) to characterize Gem pharmacokinetics. PBMCs and tissue biopsies pre treatment and during cycle 1 were collected to characterize the effect of Gem + FTS on levels of activated Ras protein. Treatment efficacy was assessed every other cycle. Results: Thirteen patients (8 male, 5 female, ages 40 to 80, ECOG 0–1) are enrolled to date. The most common adverse events were neutropenia, anemia, abdominal cramping, elevated liver function tests and diarrhea. At the time of this analysis, the progression free survival for these 13 patients is 4.7 months with median survival of &gt;10.8 months and 1 year survival of 50%. Conclusions: 1. Salirasib in combination with gemcitabine appears to be safe with no PK interaction. 2. Salirasib in combination with gemcitabine at doses to 800 mg b.i.d. did not reach conventional MTD, although dose related diarrhea suggests better tolerance at doses up to 600 mg b.i.d. 3. Salirasib at doses of 400 to 800 mg b.i.d. in combination with gemcitabine demonstrated a PFS, MS and 1 year survival of 4.7 months, &gt;10.8 months and 50% respectively. 4. Salirasib mechanism of Ras inhibition is confirmed by reduction of tumor Ras in pancreatic cancer patients. 5. Salirasib warrants evaluation in a controlled study with gemcitabine in pancreatic cancer; doses of 600 or 400 mg b.i.d. are recommended. No significant financial relationships to disclose.
334. Tailoring the Size of Inter-Cistronic Spacer Sequence Significantly Increases IRES-Dependent Second Gene Expression over Cap-Dependent Expression in a Bicistronic Vector: Construction of Optimized 5′-hLDLR-IRES-eGFP-3′ Cassette for Gene Therapy of Familial Hypercholesterolaemia
Journal: Molecular Therapy (2009)
The use of an oxygen concentration 50% above baseline before and after endotracheal suctioning prevents hypoxemia in stable patients
Authors: Bruno Pessoa, Gisele Diniz, Pedro Figueiredo
Journal: European Respiratory Journal (2011)

Objective: Few are known about the use of inspired fractions of oxygen less than 100% (1) to prevent hypoxemia during endotracheal suctioning (ES). The objective was compare the repercussions of using a FiO2 50% above the baseline with a FiO2 of 100% during ES in mechanically ventilated patients.

Methods: A randomized trial in 17 patients (55,7±23,9 years) underwent 2 sessions of ES (break of 6 hours) with prior hyperoxygenation by two values of FiO2: 50% above the baseline and 100%. The heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO2) and breath rate (BR) were recorded at baseline, 5 minutes after adjusting the FiO2, likewise 1 and 5 minutes after the end of procedures.

Results: SpO2 within the groups increased in all phases of the two protocols, compared to baseline. There was an increase in HR at 1 min after ES in protocol with raising the FiO2 to 50%, compared to PRE time and baseline, as well as the BR in procedure with FiO2 of 100%. Already MAP increased only at 1o min compared to baseline in the protocol with increase FiO2 to 50%. In the intergroup analysis, SpO2 and BR was higher in the procedure with FiO2 of 100% at 1 min after the ES, but without clinical relevance.

Conclusion: The use of a FiO2 50% above baseline before and after ES prevented hypoxemia and negative changes in vital signs of stable patients on mechanical ventilation.
Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib
Authors: B. I. Rini, G. T. Wilding, G. Hudes, W. M. Stadler, S. Kim, J. C. Tarazi, P. W. Bycott, K. F. Liau, J. P. Dutcher
Journal: Journal of Clinical Oncology (2007)

5032 Background: Sunitinib and sorafenib, tyrosine kinase inhibitors (TKIs) of the VEGF and PDGF receptors (VEGFR, PDGFR), are FDA-approved treatments for advanced RCC. AG is a potent inhibitor of VEGFRs 1, 2 &amp; 3 and showed substantial efficacy in a previous phase II study in pts with cytokine-refractory RCC (Rini et al. ASCO 2005). The activity of AG in metastatic RCC patients refractory to prior TKI therapy is of interest. Methods: Pts with sorafenib-refractory RCC were enrolled in this multicenter, open-label, phase II study. Eligibility criteria included measurable disease, ECOG performance status of 0 or 1, controlled CNS metastases (if present) and adequate organ function. All pts received a starting dose of AG 5 mg orally BID, titrated according to tolerance. The primary endpoint was RECIST-defined objective response (OR) with a null hypothesis of OR = 8% versus = 20% under the alternative hypothesis. Pts underwent radiographic staging at baseline and every 8 weeks and were treated until progressive disease or unacceptable toxicity. Results: All planned 62 pts have been enrolled. Median age of 42 evaluable pts was 60 years (range 35–77); 29 pts (69%) were male; 41 pts (98%) had prior nephrectomy. Median number of prior therapies was 2 (range 1–8); all pts had received prior sorafenib and 9 pts also received prior sunitinib. Partial response was observed in 6/42 evaluable pts (14%; 95% CI: 5–29%), stable disease in 15 pts (36%), 12 pts (29%) experienced progressive disease, and 9 pts (21%) withdrew due to adverse events. Overall, 57% of pts experienced some degree of tumor regression. With a median follow-up of 5.3 months, the median progression-free survival (PFS) was not reached. Preliminary analysis indicates overall median PFS &gt; 7.1 months. No ORs have yet been observed in patients with prior sunitinib treatment, although tumor regression was demonstrated in 55% of pts with median PFS &gt; 6.1 months. Treatment-related grade 3/4 AEs included hypertension (16%), fatigue (14%) and hand foot syndrome (14%). Overall, 36 pts remain on study. Conclusions: AG has substantial antitumor activity in pts with sorafenib-refractory, metastatic RCC. Toxicity is typical of TKI VEGFR inhibitors and generally manageable. [Table: see text]
Immunotherapy by Intralesional Injection of BCG Cell Walls or Live BCG in Bovine Ocular Squamous Cell Carcinoma: A Preliminary Report&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: W R Klein, E J Ruitenberg, P A Steerenberg, W H de Jong, W Kruizinga, W Misdorp, J Bier, R H Tiesjema, J G Kreeftenberg, J S Teppema, H J Rapp
Journal: JNCI Journal of the National Cancer Institute (1982)

Cows of the Dutch Frisian and Maas-Rijn-IJssel breed with histologically confirmed ocular squamous cell carcinoma showed complete regression of the primary tumor in 70 or 60% of the cases after intralesional injection of a BCG cell wall or live BCG vaccine, respectively. Recurrence of the tumor was observed in 57% of the animals treated with BCG cell walls and in 25% of the animals treated with live BCG vaccine. Spontaneous regression was seen in 20% of the untreated cows. In a second control group, radical surgery, the most successful treatment for primary stage I tumors in humans, resulted in a 90% cure. Influence of immunotherapy on metastases could not yet be fully evaluated. White blood cell counts were not changed after therapy. It was not possible to link a favorable response to BCG therapy with the intensity of the delayed type hypersensitivity (DTH) reaction to purified protein derivative of mycobacteriae (PPD) or the formation of antibodies to BCG as determined by a micro-enzyme-linked immunosorbent assay. However, in animals that showed tumor regression, the DTH reaction to PPD had a tendency to persist for a longer period of time. It was concluded that 1) block resection was the best method of treatment for this tumor, 2) a single intralesional injection of a BCG cell wall vaccine was as effective as live BCG vaccine in the induction of complete regression of the primary tumor, 3) in this preliminary study BCG cell wall vaccine was less effective than live BCG vaccine in the prevention of recurrence, and 4) this naturally occurring tumor model is well suited for the study of the influence of BCG immunotherapy in a primary stage I tumor.