tbuckley/cabot-search huggingface dataset:
The biology and treatment of superficial bladder cancer.
Authors: F M Torti, B L Lum
Journal: Journal of Clinical Oncology (1984)

Management of the superficial bladder cancer patient consists of two complementary but separate therapeutic goals: treatment of the existing tumor(s) and prevention of tumor recurrence. At present, the stage, grade, and multicentricity are the major determinants in the natural and therapeutic history of the disease. Although intravesical instillation of chemotherapeutic agents has been used for greater than 20 years, neither its exact role nor the optimal dose or schedule of administration have been established. To date, no dramatic differences in efficacy between the agents commonly used for intravesical chemotherapy, either as definitive therapy or prophylaxis, have been appreciated. These agents do appear to lower the recurrence rate as well as extend the disease-free interval. Since the most thorough experience is with thiotepa, it is the drug against which other agents should be compared in terms of both efficacy and toxicologic evaluation. Different administration schedules and methodologies need further study, such as the utility of continuous bladder irrigation, the use of sequential chemotherapeutic agents to gain cell synchronization, and the use of multiple drug regimens. Because there are multiple factors that influence the occurrence and recurrence of bladder cancer, combined modality therapy deserves testing. Modes of therapy that could be used together because they act through different mechanisms are intravesical chemotherapy, radioactive needle implants, carcinogen modifiers such as pyridoxine, chemoprotective agents such as retinoic acid, and immune stimulants such as BCG. These studies should be performed in a randomized prospective controlled fashion, which may require cooperative multi-institutional involvement to accrue adequate numbers of patients. At this time there are a number of important questions that remain to be answered concerning the treatment of superficial bladder cancer: (1) does this mode of therapy affect overall survival, (2) does prophylactic intravesical chemotherapy alter the incidence of subsequent muscle invasive disease, (3) does intravesical chemotherapy alter the sites, incidence, or responsiveness to systemic chemotherapy of subsequent metastatic disease, and (4) and what is the optimal timing and duration of prophylactic therapy from a cost-effectiveness standpoint?
ARG2 and NOS2 as predictive biomarkers in renal cell carcinoma
Authors: Virginia White, Lucio Miele, John Estrada, Jennifer Cvitanovic, Arnold Zea
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts There is a great deal of variability in the survival of patients diagnosed with renal cell carcinoma (RCC) that is not explained by the classical clinic-pathological measures of aggressiveness such as tumor stage or tumor grade. There is an urgent need to identify more accurate
Bone marrow transplantation of chronic myelogenous leukemia in chronic phase: evaluation of risks and benefits.
Authors: J E Wagner, M Zahurak, S Piantadosi, R B Geller, G B Vogelsang, J R Wingard, R Saral, C Griffin, N Shah, B A Zehnbauer
Journal: Journal of Clinical Oncology (1992)

Allogeneic bone marrow transplantation (BMT) is an option for some patients with chronic myelogenous leukemia (CML). We retrospectively evaluated the effect of various risk factors observed at diagnosis and at transplantation on survival, event-free survival (EFS), and relapse after BMT.Seventy-nine patients with CML in chronic phase (CP) were treated with cyclophosphamide and total body irradiation followed by BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CsA) in most instances or CsA plus the use of lymphocyte-depleted bone marrow (BM).Survival at 4.5 years was 52%. Stratified by age and GVHD prophylaxis, the actuarial survival was 65% (95% confidence interval [CI], 47% to 78%) in patients aged less than 30 years receiving unmanipulated BM, 33% (95% CI, 12% to 56%) in patients greater than or equal to 30 years old receiving unmanipulated BM, and 38% (95% CI, 14% to 63%) in patients greater than or equal to 30 years old receiving lymphocyte-depleted BM. In univariate analysis, patient age (greater than or equal to 30 years) and the use of lymphocyte-depleted BM negatively influenced EFS. When stratified by age and GVHD prophylaxis, however, ABO incompatibility, cytomegalovirus (CMV) seropositivity, and chronic GVHD significantly reduced the probability of EFS. Factors that have been associated with early death in nontransplanted patients (ie, sex, spleen size, blast and platelet counts at presentation) were not predictive of long-term survival outcome after BMT.The data suggest that (1) BMT should be offered early after diagnosis to all patients with CML in CP who have compatible sibling donors regardless of prognostic factors at presentation, (2) GVHD remains the principal cause of mortality after BMT in patients receiving CsA, and (3) T-cell depletion by the physical separation method of counterflow elutriation (CE) is associated with a significant risk of relapse.
Effects of cloned human leukocyte interferons in the human tumor stem cell assay.
Authors: S E Salmon, B G Durie, L Young, R M Liu, P W Trown, N Stebbing
Journal: Journal of Clinical Oncology (1983)

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
Abstract P220: Sustained Disparity in Ever Having Received a Serum Cholesterol Measurement by Educational Level among US Adults, 1999-2012
Authors: Otome Kinoshita, Takehiro Sugiyama, Tetsuro Tsujimoto, Martin F Shapiro, Yasuki Kobayashi
Journal: Circulation (2015)

Background: A previous study showed that lower educational level was significantly associated with less likelihood of ever having received a serum cholesterol test among US adults during 1999-2002. No study, however, has examined the time trends after 2002. Objectives: To examine whether disparity by educational level in lifetime receipt of a serum cholesterol test persisted in the US from 1999 through 2012. Methods: A serial cross-sectional study in a nationally representative sample of 29,662 US adults from the National Health and Nutrition Examination Survey, 1999-2012. We excluded those had coronary heart disease and/or diabetes. The lifetime history of having had a serum test for cholesterol and educational level were asked in the interview. Educational level was grouped as greater than high school (HS), HS, or less than HS. We investigated time trends of lifetime cholesterol measurement by educational level, using a logistic regression model that included interaction terms between survey period and educational level, adjusted for covariates. Results: In 1999-2000, the proportion of ever having had a serum cholesterol test was significantly lower for participants with less education (greater than HS: 76.2%, HS: 62.0%, less than HS: 51.4%). In 2011-2012, the pattern of lifetime testing by educational level was similar to the initial period (greater than HS: 77.5%, HS: 67.5%, less than HS: 55.4%). Although the uptake of cholesterol testing significantly increased over the survey period among the less-than-HS group, the difference in trends across the three groups was not significant. Conclusions: The difference by educational level in lifetime serum cholesterol measurement observed in 1999-2002 persisted through 2011-2012. Public health policy should focus on increasing the uptake of serum cholesterol test and early detection of hypercholesterolemia, particularly among people with lower educational level. Figure. Trends of lifetime serum cholesterol measurement by educational level among US adults, 1999-2012
Antisense Oligonucleotides for Duchenne Muscular Dystrophy
Authors: Ryan D. Jacobson, Eva L. Feldman
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
LE-SN38 for metastatic colorectal cancer after progression on oxaliplatin: Results of CALGB 80402
Authors: A. J. Ocean, D. Niedzwiecki, J. N. Atkins, B. Parker, B. H. O’Neil, J. W. Lee, S. Wadler, R. M. Goldberg
Journal: Journal of Clinical Oncology (2008)

4109 Background: In patients (pts) with metastatic colorectal cancer (mCRC) after first-line progression on 5-fluorouracil (5-FU), irinotecan (IRI) improves survival over best supportive care or additional 5-FU. IRI provides limited survival benefit, commonly causes asthenia and diarrhea, and rarely causes fatal toxicities related to dehydration and sepsis. LE-SN38 is a liposomal formulation of SN38, the active metabolite of IRI. LE-SN38 was formulated in an attempt to improve the therapeutic index of IRI by preserving clinical activity without increasing overall toxicities. This single arm, open label Phase II study assesses the response rate (RR) and toxicity profile of LE-SN38 in pts with mCRC. Methods: Pts had histologically or cytologically confirmed mCRC, measurable disease, and received one prior 5- FU/oxaliplatin (but not IRI) regimen for metastatic disease. Pts had ECOG PS 0–1, normal bone marrow, hepatic, and renal function. UGT1A1 genotype status was determined prior to registration and pts were eligible if homozygous for wild-type UGT1A1*1 or heterozygous for UGT1A1*28. Pts received LE-SN38 35mg/m2 IV over 90 min every 21 days until disease progression for a minimum of 2 cycles. Tumor assessment by imaging was done every 2 cycles. The primary endpoint of this trial was RR. A RR of 15%, comparable to that of irinotecan, was considered worthy of further study. Results: 30 pts (16 males, 14 females) were enrolled and treated from 1/06–1/07. Median age was 50–59y. Toxicities included Grade 4: leukocytes (7%), neutrophils/granulocytes (7%). Grade 3: hemoglobin (3%), lymphopenia (3%), neutrophils/granulocytes (7%), prothrombin time (PT) (3%), nausea (3%), gastrointestinal obstruction (3%), vomiting (3%), pain (3%). There was no Grade 3–4 diarrhea. There were no complete (CR) or partial responses (PR), but 11 pts had stable disease (SD) observed. Median PFS was 1.58 months (95% CI: 1.51, 2 months) and median OS was 9.07 months (95%CI: 6.67, 11.27 months). Conclusions: LE-SN38 did not meet the prespecified activity criteria for OR and PFS. Although LE-SN38 is associated with an acceptable toxicity profile, this formulation, dose and schedule of LE-SN38 does not merit further evaluation in previously treated pts with mCRC. No significant financial relationships to disclose.
Treatment and prognosis of epithelial ovarian cancer in Iran
Authors: R. Khodabakhshi, S. Yahyazadeh Jabbari, M. Gohari, B. Sadrolhefazi, A. Mosavizadeh, J. Shahidi, A. Ameri, H. Madani, B. Sharifi, F. Bahor
Journal: Journal of Clinical Oncology (2007)

5586 Background: Ovarian cancer is the most lethal gynecologic malignancy in the US, with 14,500 women dying of this disease annually. The aims of this study are to describe brief epidemiologic variations, response rate for usual chemotherapy regimen and progression free survival analysis in Iranian patients. Patients and Methods: 98 women with confirmed ovarian cancer who have been undergone surgery followed by chemotherapy at three hospitals in Tehran (Iran) between 1997 and 2003 were enrolled in this retrospective study. FIGO staging system has been applied. We have collected data regarding age, pathologic variations, surgical procedure (complete, partial, biopsy), chemotherapy, response rate, and time to progression of disease. Results: From a total of 98 patients, there were 80 (81.6%) epithelial, 12 (12.2%) germ cell, 5 (5.1%) granulosa cell tumors and one case of lymphoma. Response rate have been evaluated for 60 patients with epithelial cancer. Overall mean age was 46.7 and average age for epithelial tumors and non-epithelial tumors were 49.6 and 34.3 respectively. Complete surgical procedure with staging and optimal residue had been performed for 18 patients. Stage III was the most common stage (46.1%). In 78.3% of patients complete or partial response were seen, while 21.7% of patients showed stable or progressive disease. The most important prognostic factors were stage, and extent of surgical procedure. Median progression-free survival was 24.2 months. Conclusion: Overall average-age of our patients is lower than expected. Besides, a large proportion of the patients are referred in advanced stages. Although, higher response rate has been produced by taxane-based regimen in comparison of traditional chemotherapy; but it was not statistically significant. Retrospective evaluation, low number of the patients, non-uniform usage of chemotherapy regimen could influence our results. No significant financial relationships to disclose.
Prevalence, severity, and evolution of anemia in colorectal cancer patients receiving radiation therapy with/without chemotherapy: a retrospective analysis
Authors: K. Hu, D. Shasha, P. Homel, L. B. Harrison
Journal: Journal of Clinical Oncology (2006)

13510 Background: Colorectal cancer (CRC) patients frequently present with anemia. Anemia may also develop or be exacerbated in CRC patients as a consequence of treatment with radiation therapy (RT) with or without (±) chemotherapy (CT). A better understanding of the relationship between anemia and RT ± CT is important as several studies have found that hemoglobin (Hb) levels are predictive of RT outcomes and that low Hb levels can diminish patient quality of life (QOL). However, the prevalence and evolution of anemia before and during RT ± CT are poorly characterized in CRC patients. Methods: Prospectively collected data from 81 CRC patients who received 10 weeks of curative-intent RT alone (26%) or in combination with CT (74%) were analyzed retrospectively to determine prevalence, severity, patterns and contributing factors of anemia. Results: Prior to RT ± CT, 38% of patients (n = 71, evaluable population) were anemic (defined as Hb ≤12 g/dL) and by the end of treatment, 61% were anemic (including 41% of patients not anemic and 93% anemic pre-treatment). A significant (P &lt;.001) decrease in mean Hb for all patients was already apparent after &lt;5 weeks RT ± CT, ie, from 12.6±2.0 g/dL to 11.5±1.8 g/dL, and the decrease in Hb remained consistent over time (see Table). The greatest Hb decrease was noted in patients not anemic pre-treatment, although not all became anemic. Multivariate analysis using logistic regression identified pre-treatment anemia (P = .0006) and age (P = .02) as the factors most strongly associated with intra-treatment anemia. Conclusions: Because anemia can adversely affect QOL and possibly also treatment outcomes in cancer patients, this condition needs to be addressed as part of the overall management of anemic colorectal cancer patients. [Table: see text] [Table: see text]
<sup>90</sup>y-ibritumomab tiuxetan followed by reduced-intensity conditioning (RIC) and allogeneic stem-cell transplantation (SCT) in patients with high-risk relapsed, refractory, or transformed follicular lymphoma (FL).
Authors: K. Abou-Nassar, K. Stevenson, J. H. Antin, A. Freedman
Journal: Journal of Clinical Oncology (2010)

6538 Background: The use of RIC SCT in relapsed, refractory or transformed FL is associated with higher relapse rates but similar overall survival (OS) when compared to myeloablative SCT. Radioimmunoconjugates prior to RIC allogeneic SCT may provide sufficient early cytoreduction while allowing for long-term disease control through graft versus lymphoma effect without the associated toxicity of a myeloablative SCT in this older, often heavily pretreated patient population. Methods: We performed a retrospective study to describe the baseline characteristics and outcomes of twelve patients with relapsed, refractory or transformed FL who received 90Y ibritumomab tiuxetan followed by fludarabine and low-dose busulfan RIC allogeneic SCT at the Dana-Farber Cancer Institute between 2006 and 2009. Results: Twelve patients were identified with a median age of 55 (40-66) years and a median number of lines of therapy of 5 (2-10). Three (25%) had chemorefractory FL and two (17%) had transformed to a more aggressive histology. Nine patients (75%) received SCT from unrelated donors. The median follow-up is 24 months (range, 3-42). The median time from 90Y ibritumomab tiuxetan to SCT was 1.0 month (range 0.4-5.8). Two (17%) and four (33%) patients did not reach a nadir for PMN and platelets, respectively. All patients engrafted with a median time to PMN and platelet engraftment of 14 days (n = 10; range 11-35) and 20 days (n = 8; range 11-163), respectively. Conclusions: Ten patients (83%) achieved a complete response (CR) and two patients achieved a partial response (PR). Two patients died from infection (n = 1) and graft versus host disease (GVHD) (n = 1). One patient relapsed. Cumulative incidences of grade II-IV acute GVHD at 200 days were 28% (± 15%) and chronic GVHD at 12 months were 67 % (± 18%). Two-year non-relapse mortality was 20% (± 14%). Two-year OS and progression-free survival were 80% (± 13%) and 69% (± 15%), respectively.This treatment is associated with favorable outcomes including acceptable rates of GVHD and relapse in this high-risk patient population and warrants prospective studies. No significant financial relationships to disclose.
Exploring the Phenotypic Space and the Evolutionary History of a Natural Mutation in<i>Drosophila melanogaster</i>
Authors: Anna Ullastres, Natalia Petit, Josefa González
Journal: Molecular Biology and Evolution (2015)

A major challenge of modern Biology is elucidating the functional consequences of natural mutations. Although we have a good understanding of the effects of laboratory-induced mutations on the molecular- and organismal-level phenotypes, the study of natural mutations has lagged behind. In this work, we explore the phenotypic space and the evolutionary history of a previously identified adaptive transposable element insertion. We first combined several tests that capture different signatures of selection to show that there is evidence of positive selection in the regions flanking FBti0019386 insertion. We then explored several phenotypes related to known phenotypic effects of nearby genes, and having plausible connections to fitness variation in nature. We found that flies with FBti0019386 insertion had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested. Indeed, a global analysis of the population frequency of FBti0019386 showed that climatic variables explain well the FBti0019386 frequency patterns only in Australia. Finally, although FBti0019386 insertion could be inducing the formation of heterochromatin by recruiting HP1a (Heterochromatin Protein 1a) protein, the insertion is associated with upregulation of sra in adult females. Overall, our integrative approach allowed us to shed light on the evolutionary history, the relevant fitness effects, and the likely molecular mechanisms of an adaptive mutation and highlights the complexity of natural genetic variants.