tbuckley/cabot-search huggingface dataset:
Oblimersen 1-hour IV infusion in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma.
Authors: P. A. Ott, K. M. Madden, R. Kannan, H. Yee, S. Mendoza, B. Dubose, L. Liebes, A. C. Pavlick
Journal: Journal of Clinical Oncology (2010)

8561 Background: Oblimersen (OBL), temozolomide (TMZ), and albumin-bound paclitaxel (ABP) are synergistic in melanoma cell lines. We recently reported promising results with this regimen in 18 patients with advanced melanoma and normal LDH. OBL was given as a 7-day continuous IV infusion (7 mg/kg/d, day 1-7, 22-28) in combination with TMZ (75 mg/m2/d, day 1-42) and ABP (175 or 260 mg/m2, day 7, 28 after OBL) in 56-day cycles. Response rate (33%) included 1 CR lasting > 25 months and 5 PRs lasting > 2 cycles. Seven pts (39%) had SD > 3 cycles and 5 (28%), disease progression. Based on the safety profile and PK of OBL given by short IV infusion, we evaluated a fixed dose of OBL given as a 1-hour IV infusion with TMZ and ABP. Methods: Chemotherapy-naïve patients with advanced melanoma, ECOG PS ≤ 2, and baseline LDH ≤ 1.1 × ULN received TMZ 75 mg/m2/d orally (day 1-42), OBL 900 mg as a 1-hour IV infusion (days 1,4,8,11,22,25,29,32), and ABP 175 mg/m2 as a 30-minute IV infusion (days 4,25) in 56-day cycles. Responses were evaluated per RECIST. Blood samples were obtained for OBL and ABP PK, and measurement of serum shed cryptic epitopes. Immunohistochemistry (IHC) staining for Bcl-2, Bcl-XL, BAK, and caspase 3 was performed on days -1, 4, and 28 tumor samples. Results: Ten patients have been treated with the OBL one-hour infusion. Two patients progressed after one cycle. Eight patients are continuing treatment; 3 have a PR, 4 have SD and one has not been evaluated yet. One patient with a PR demonstrated increased intra-tumoral caspase 3 and decreased Bcl-2 on day 4 due to an overall reduction in tumor burden, which correlated with a decrease in shed collagen epitopes and clinical response. The one-hour OBL IV infusion has been well tolerated. No grade 3 or 4 events other than a grade 3 preexisting pleural effusion have occurred. Planned enrollment of 14 pts is continuing. Conclusions: Preliminary data from this ongoing study appear to confirm the promising response and disease-control rates observed with this drug combination using a substantially more convenient dosing regimen. The OBL 1-hour IV infusion is well tolerated in combination with TMZ and ABP. Additional clinical data, as well as PK and IHC data, will be presented. No significant financial relationships to disclose.
Benefit of rituximab combined to ACVBP (R-ACVBP) over ACVBP in 209 poor- risk BDLC NHL patients treated with up-front consolidative autotransplantation: A GELA phase II trial (LNH 2003–3)
Authors: N. Mounier, C. Gisselbrecht, O. Fitoussi, K. Belhadj, P. Feugier, B. Coiffier, H. Tilly, O. Casasnovas, C. Fermé, J. Briere, C. Haioun
Journal: Journal of Clinical Oncology (2009)

8507 Background: Rituximab (R) combined with CHOP improves survival in DLBCL pts. More intensive regimen followed by auto transplantation have been used in patients &lt; 60y with 2–3 adverse age-adjusted International-Prognostic-Index (aa-IPI) factors, providing a 5y OS of 65% (CI 60–68%), (Haioun LNH 98–3B, ASCO 2007). The objective of the present study was to assess whether or not combining R (375 mg/m2) to the dose intense ACVBP (doxorubicin 75 mg/m2 d1, cyclophosphamide 1,200 mg/m2 d1, vindesine 2 mg/m2 and bleomycin 10 mg d1 and d5, prednisone 60 mg/m2 d1-d5) also translates into a survival benefit. Methods: From 01/2004 to 12/2005, 209 DLCBL pts &lt; 60y with DLBCL and aaIPI 2 or 3 received 4 cycles of R-ACVBP every 15 days. CR and PR pts received a consolidative BEAM and peripheral blood stem cell rescue (LNH2003–3 trial, # NCT00144807 ). Median age was 49 years, 22 % of patients presented with aa-IPI 3, 58% with IPI 3–5 (93% with elevated LDH and 54 % with extranodal sites &gt;1). CR rate after induction was 61%, PR rate 24% leading to an overall response rate of 84% (176 pts). Collection failure was observed in 18 pts (10%). 155 pts received auto transplantation, representing 75% of the study population. Results: With a median follow-up of 27 months, according to the updated IWC 2007, 3y PFS and OS were estimated at 76% (CI 69–81%) and 81% (CI 75–86%), respectively. A case-controlled study was performed by matching the present R-ACVBP population with ACVBP patients selected from the LNH-98–3 trial. Patients were fully matched (1:1) on histology, aa-IPI score, gender, age and follow-up duration. 3y PFS was higher in R-ACVBP than in ACVBP patients: 75% (CI 67–81%) vs 58% (CI 50–65%), p=0.0003. 3y OS were estimated at 78% (CI 71–84%) vs 67% (CI 58–74%), p=0.05. The gain in 3y OS was significant in patients who received auto transplantation: 89% (CI 81–93%) vs 77% (CI 67–84%), p=0.02. Conclusions: These results with R-ACVBP induction and consolidative auto-transplantation suggest a major survival benefit which needs confirmatory prospective study. No significant financial relationships to disclose.
Serum Haptoglobin Type and Cancer
Authors: M F Larkin
Journal: JNCI Journal of the National Cancer Institute (1967)

The distribution of haptoglobin types in 526 cancerous and 430 noncancerous subjects is presented. The frequency of haptoglobin 1 gene, in females, ranged sequentially from 0.264 in patients with cancer of the cervix, uterus, and ovary, through melanoma, breast cancer, cancer of the colon, to 0.467 in reticuloses. This was supported by statistically significant differences observed between some groups of cancer patients and normal controls. A different haptoglobin 1 gene frequency was found for male cancer patients.
Primary lung sarcomas. The Mayo Clinic experience
Authors: D. G. Perez, M. C. Aubry, J. R. Molina, R. S. Marks, S. Okuno, P. Yang
Journal: Journal of Clinical Oncology (2004)

7370 Background: Primary lung sarcomas are rare tumors accounting for 0.013% to 0.4% of all lung malignancies. It is estimated that 1 in 500 primary lung malignancies is a sarcoma. At our institution, primary lung sarcomas represent 0.6% of lung cancers. With less than 250 patients reported in the English medical literature, very little is known about the clinical behavior and treatment of these tumors. The primary goal of this study was to review the Mayo Clinic experience with this rate tumors. Methods: All cases of primary lung sarcomas seen at the Mayo Clinic from 1976 to 2002 were reviewed. Medical records were analyzed for demographic information as well as for survival and treatment data. Pathology specimens were reviewed to confirm the diagnosis of primary lung sarcoma. Results: A total of 65 cases of primary lung sarcoma were found during the last 52 years at Mayo Clinic. Most patients presented with persistent respiratory symptoms such as chest pain, cough, hemoptysis and dyspnea. Hypoglycemia, which has been described in patients with this malignancy, was seen only in one patient with a very large tumor. The main duration of symptoms at the time of diagnosis was 2 months. The presence of an infiltrate or a mass was the most common finding (90%). In most cases, the tumor was more than 5 cm in diameter (65%). Surgery was the main treatment modality (lobectomy 70%, wedge resection 20%, and pneumonectomy 10%). Radiation as the only treatment modality was used in 18% of patients. Adjuvant chemotherapy or radiation was used in 30% of cases. Relapses were treated with surgery followed by chemotherapy and radiation or both. Survival was estimated to be 30 months. Conclusions: Diagnosis of primary lung sarcoma requires careful exclusion of primary sarcoma elsewhere. Surgical resection, if complete, is curative for small, well-differentiated primary lung sarcomas. Poorly differentiated tumors are less curable, but resection may provide palliation and should be considered. Unresectable or recurrent sarcomas may be treated with radiation therapy or chemotherapy, although responses are usually brief and survival is less than 1 year. No significant financial relationships to disclose.
MOPC-315 Murine Plasmacytoma as a Model Anticancer Screen for Human Multiple Myeloma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F Valeriote, H Grates
Journal: JNCI Journal of the National Cancer Institute (1986)

The murine tumor MOPC-315 plasmacytoma was studied as a model for human multiple myeloma. Plasmacytoma cells (106) were injected iv into BALB/c mice, and 14 days later a single ip dose of the anticancer agent to be tested was administered at a dose that would result in 10% toxicity within 30 days (LD10). Increases in life-span and cures resulting from the LD10 dose were the parameters assessed. The response of this MOPC-315 plasmacytoma model to a variety of anticancer agents demonstrated good correlation with clinically active agents. A number of investigational agents were found to be highly active and potential candidates for clinical phase II studies.
Increased toxicity associated with delayed clearance of methothrexate (MTX) in patients with lymphoma receiving high-dose MTX
Authors: A. Huen, J. E. Romaguera, L. E. Fayad, S. R. Teegala, Y. Ji, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2007)

19578 Background: High response rates have been observed with the rituximab (R), cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HyperCVAD) alternating R-MTX and cytarabine(AraC) regimen in patients with mantle cell lymphoma (MCL). Delayed MTX clearance, related to high dose MTX (1gm/m2) used in this regimen, is an important problem since the common practice is to monitor patients in the hospital for leucovorin rescue, hydration and urine alkalinization to avoid potential toxicity. It is unclear, however, if moderate delay in clearance is associated with increased toxicity. Methods: In this retrospective cohort study, we analyzed toxicity data from pts with MCL who received R-MTX (1gm/m2 given intravenously over 24 hours)/Ara-C as part of the R-HyperCVAD regimen. Delayed MTX clearance was defined as serum MTX level ≥ 0.1 μmol/L at 48 hours after end of infusion. Results: 112 patients received a total of 232 cycles of the (R)MTX/Ara-C regimen. The median age was 61 years (range, 40–80) with 37% of patients over 65 years. Of the 228 evaluable cycles, 80 cycles (35 %) had delayed MTX clearance. Median time to clearance of MTX in the delayed clearance group was 72 hours post treatment (range 72–336 hours). Serum MTX levels at 48 hours from MTX completion in the delayed group ranged from 0.1 to 3.55 micromol/L. The cycles with delayed MTX clearance were associated with more toxicity than cycles with non-delayed clearance as shown in the table below. *(out of 143 evaluable cycles) Conclusions: These findings indicate that patients with delayed MTX clearance at 48 hours are at increased risk for myelosuppression and renal toxicity. These findings suggest future evaluation of the role of Carboxypeptidase (CPDG2), a novel enzyme that cleaves MTX into inactive metabolite, for early intervention in patients with an evidence of delayed clearance at 48 hours to reduce hospitalization and prevent subsequent complications. [Table: see text] No significant financial relationships to disclose.
More is better.
Authors: W M Hryniuk
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.9.1365 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3047331 More is better. W M HryniukxW M HryniukSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.9.1365 First Page PDF © 1988 by American Society of Clinical Oncology
Abstract 18986: Low Density Lipoprotein Cholesterol Response and Statin Persistence among Patients with High Coronary Heart Disease Risk Initiating Treatment
Authors: Suma Vupputuri, Peter J Joski, Ryan Kilpatrick, Michael Woolley, Brandi E Robinson, Michael E Farkouh, Huifeng Yun, Monika M Safford, Paul Muntner
Journal: Circulation (2014)

The 2013 American College of Cardiology/American Heart Association cholesterol treatment guideline recommends monitoring percent reduction in low density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. We examined LDL-C reduction and statin persistence among high risk patients initiating statins in a real-world setting. This retrospective cohort study included 1,066 Kaiser Permanente Georgia members with a history of coronary heart disease or risk equivalent(s) initiating statins in 2011. Percent change in LDL-C was defined using measurements before and 60-450 days after statin initiation. Statin persistence was defined by proportion of days covered and categorized as high (≥80%), intermediate (50-79%), and low (&lt;50%). Overall, 58.4% of patients failed to achieve a ≥30% LDL-C reduction after statin initiation. The prevalence of high, intermediate and low statin persistence was 41.3%, 23.2%, and 35.6%, respectively. Of patients with high persistence, 42.3% did not achieve a ≥30% reduction in LDL-C compared with 54.7%, and 79.7% of those with intermediate and low statin persistence, respectively. After multivariable adjustment and compared to high persistence, the risk ratio for a low LDL-C reduction was 1.31 (95%CI: 1.13,1.52) for intermediate persistence and 1.88 (95%CI: 1.67,2.11), for low persistence. Women and African-Americans were less likely to have high persistence while having cardiologist follow-up visits was associated with high persistence. Also, after multivariable adjustment, patients with an LDL-C ≥ 100 mg/dL versus &lt; 100 mg/dL were less likely, while those initiating therapy with pravastatin were more likely to have a ≥30% reduction in LDL-C. In a real-world setting, many patients initiating statins did not achieve a 30% or larger LDL-C reduction. These data support the ACC/AHA recommendation to monitor LDL-C response among patients initiating statins.
Immunotherapy Combined or Sequenced With Targeted Therapy in the Treatment of Solid Tumors: Current Perspectives
Authors: Michael B. Atkins, James Larkin
Journal: JNCI Journal of the National Cancer Institute (2016)

The advent of newer immunotherapeutic and molecularly targeted agents has provided a number of effective options for cancer treatment but has also added much complexity in selecting the best initial treatment or treatment plan for each patient. Molecularly targeted agents offer selectivity and are the cornerstone for "precision medicine." While targeted agents are associated with high tumor response rates, patients inevitably develop resistance to these drugs. Immunotherapies exploit the endogenous immune system to eradicate cancer and can produce durable disease control that results in long-term, treatment-free survival in some patients. Guidelines for treatment selection in patients with specific tumor types and clinical features are routinely being reconsidered in order to accommodate the increasingly complex treatment landscapes. Here, we review current perspectives on the use of immunotherapeutic agents, particularly immune checkpoint inhibitors (nivolumab, pembrolizumab, and ipilimumab), in combination or in sequence with molecularly targeted agents in patients with advanced melanoma as well as other tumor types. We further discuss remaining unmet needs for patient selection and treatment with approved therapies.
Angiotensin II Activates Collagen Type I Gene in the Renal Cortex and Aorta of Transgenic Mice through Interaction with Endothelin and TGF-β
Authors: Fadi Fakhouri, Sandrine Placier, Raymond Ardaillou, Jean-Claude Dussaule, Christos Chatziantoniou
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Hypertension is frequently associated with the development of renal vascular fibrosis. This pathophysiologic process is due to the abnormal formation of extracellular matrix proteins, mainly collagen type I. In previous studies, it has been observed that the pharmacologic blockade of angiotensin II (Ang II) or endothelin (ET) blunted the development of glomerulo- and nephroangiosclerosis in nitric oxide-deficient hypertensive animals by inhibiting collagen I gene activation. The purpose of this study was to investigate whether and how AngII interacts with ET to activate the collagen I gene and whether transforming growth factor-β (TGF-β) could be a player in this interaction. Experiments were performed in vivo on transgenic mice harboring the luciferase gene under the control of the collagen I-α2 chain promoter (procolα2[I]). Bolus intravenous administration of AngII or ET produced a rapid, dose-dependent activation of collagen I gene in aorta and renal cortical slices (threefold increase over control at 2 h, P < 0.01). The AngII-induced effect on procolα2(I) was completely inhibited by candesartan (AngII type 1 receptor antagonist) and substantially blunted by bosentan (dual ET receptor antagonist) (P < 0.01), whereas the ET-induced activation of collagen I gene was blocked only by bosentan. In subsequent experiments, TGF-β (also administered intravenously) produced a rapid increase of procolα2(I) in aorta and renal cortical slices (twofold increase over control at 1 h, P < 0.01) that was completely blocked by decorin (scavenger of the active form of TGF-β). In addition, decorin attenuated the activation of collagen I gene produced by AngII (P < 0.01). These data indicate that AngII can activate collagen I gene in aorta and renal cortex in vivo by a mechanism(s) requiring participation and/or cooperation of ET and TGF-β.
Emergence of intense suicidal preoccupation during fluoxetine treatment
Authors: M H Teicher, C Glod, J O Cole
Journal: American Journal of Psychiatry (1990)

Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these patients had ever experienced a similar state during treatment with any other psychotropic drug.
Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis.
Authors: B Mellado, D Colomer, T Castel, M Muñoz, E Carballo, M Galán, J M Mascaró, J L Vives-Corrons, J J Grau, J Estapé
Journal: Journal of Clinical Oncology (1996)

PURPOSE Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P &lt; .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.
Late-breaking abstract: A case of miliary TB presenting with large pneumothorax
Authors: Ashfaq Hussain
Journal: European Respiratory Journal (2011)

A 30y old male presented to A&E with sudden onset of right sided pleuritic chest pain and acutely SOB.   Background:  Previously fit and well, Asian, born in UK, no medical problems.  Smoker 10-15 cigarettes, occasional use of alcohol, lives alone and work in a printing factory. No recent contact with ill person and no family history of lung diseases.  He has been complaining of dry cough for last two months since he returned from holidays in Spain, but did not seek any medical advice. Denies any h/o weight loss, hemoptysis, fever or rigors.  This time presented with sudden onset of sharp right sided pleuritic pain and could not breath, so brought to A&E.   Examination/Investigations:  On arrivals sats were 90%on 15l O2, tachypnic, RR30/m, clearly in respiratory distress and absent air entry on right lung, and enlarged right supraclavicular lymph node.  Emergency chest X-ray was arranged which showed large (75%) R sided pneumothorex.An emergency chest drain was inserted after failed aspiration and repeat CXR showed good expansions of the right lung and patient was referred to the medical team.  When seen by medical team his CXR showed reticulonodular changes on both lung fields, on top of the Pneumothorax, which was latter reported as pattern of miliary TB.  A sputum sample was sent for AFB, had a CT head and lumber puncture done and there was no meningeal involvement. His HIV test came back as negative and was started on anti TB treatment and so far has been doing well and making good recovery.   Learning point:  Learning point was that military TB can present with pneumothorax and one should not focus on the main abnormality on CXR which was pneumothorax in this case, but also look for other abnormalities which may be relevant to the presentation.
Airway dimensions and pulmonary phenotypes in a heavy smoking population
Authors: Akkelies Dijkstra, Dirkje Postma, Peter van Ooijen, Judith Vonk, Pieter Zanen, Michael Schmidt, Harry Groen, Firdaus Mohamed Hoessein
Journal: European Respiratory Journal (2011)

Measurements of airway dimensions using low-dose computed tomography (LDCT) may elucidate the contribution of airway and parenchymal changes to airway obstruction.  We studied the association between airway wall thickness (AWT), lung function, chronic mucus hypersecretion (CMH), emphysema and smoking behavior.  LDCT was performed in 492 male heavy smokers (59% current-smoking, packyears 34 (20-133). 39% (n=492) had COPD (GOLD-criteria) and 30% had CMH (defined: phlegm for at least 3 months a year). LDCT cross-sections at 3.5 ±.25 mm internal airway diameters were used for computerized assessment of AWT. To determine the extent of emphysema we computed for each individual the 15th percentile of the density distribution (p15). Mean AWT was log-transformed to obtain a normal distribution. Differences between COPD and non-COPD and CMH and non-CMH were tested with t-tests. Associations between AWT, FEV 1 , CMH, packyears, current-smoking, and p15 were analyzed using linear and logistic regression (adjusted for height and age).  Median AWT was increased in COPD vs non-COPD (0.72 vs 0.54 mm, p 1  and with higher p15 (i.e. less emphysema) in COPD and non-COPD. There was no significant association between AWT and CMH, packyears and current smoking in COPD and non-COPD. CMH was associated with current-smoking in COPD (OR=2.6, 95%CI=1.29-5.28) and non-COPD (OR=3.0, 95%CI=1.60-5.66) but not with packyears, p15, AWT and FEV 1 .  Thickening of the airway wall is strongly associated with decreased FEV 1  and less emphysema but not with CMH in COPD and non-COPD. Presence of CMH is associated with current-smoking.