tbuckley/cabot-search huggingface dataset:
Clinico-pathologic pattern of gastrointestinal stromal tumors (GIST) in southern India: A single-institution experience
Authors: M. Lamba, G. Mukherjee, K. Saini, C. Ramachandra, C. Rao, R. Kumar, P. Bapsy, K. Babu, S. Attili, U. Batra
Journal: Journal of Clinical Oncology (2007)

20531 Background: There have been major advances in understanding the behavioral pattern, pharmacological intervention, and clinical response of GIST; yet Indian data in this regard is sparse. This study analyses the clinico-pathologic features in 36 patients (21 male, 15 female) of GIST seen at our institution. Methods: GIST was defined as a mesenchymal spindle or epithelioid cell lesion arising in the GI tract with CD117 immuno-reactivity. Retrospective data from January 03 to March 06 was analyzed for age, tumor site, morphology, immuno- reactivity, prognostic factors, response to treatment (by RECIST), and recurrence or metastasis. All patients had surgery; those with residual, recurrent, or metastatic disease got imatinib till tumor progression. Results: GIST presented at a mean age of 48.2 yrs (SD 6.4, range 34–65). The mean tumor size was 13.9 cm (range 2–42). The most common site was the small intestine (ileum 8, jejunum 7, duodenum 4). 24 patients (66.7%) had localized disease at baseline. Of these, 14 had local recurrence after surgery, and were given imatinib. 5 of them are in complete remission, 4 had partial response (PR), 3 patients died, and 2 had stable disease. Most patients with recurrent GIST had a mitotic rate of &gt;10/50hpf. 8 patients developed metastasis, and received imatinib. Of these, 2 got a PR, 3 had progressive disease and died, and 3 had stable disease. 12 patients (33.3%) had metastasis at baseline (to liver and abdominal cavity), and underwent debulking. Of these, 6 patients with stable disease are on treatment with imatinib, 3 died and 3 were lost to follow-up. Conclusions: Average age of presentation was less than in Western reports. The commonest site was the small intestine as opposed to stomach in western literature. Mitotic rate was a better prognostic factor than gross tumor size. GIST with a mixed cell morphology showed aggressive behavior. Imatinib mesylate is useful in the post-operative management of GIST. [Table: see text] No significant financial relationships to disclose.
Expression signature of p53 status (p53 signature) for the prediction of <i>TP53 </i>mutation and prognosis in breast cancer
Authors: C. Ishioka, S. Takahashi, T. Ishida, T. Moriya, N. Ohuchi
Journal: Journal of Clinical Oncology (2006)

652 Background: The current risk evaluation criteria, such as the St. Gallen and NIH, are not sufficient for predicting which BC patients are at high risk for recurrence and mortality. The TP53 mutations are associated with worse RFS and OS, independent other risk factors in BC, but the p53 status is not simply determined and often determined incorrectly (Soussi et al. Nat Rev Cancer 2006). Our purpose was to identify the gene sets that determine expression signature of the p53 status and to correlate the gene expression profile (GEP) with clinical outcome. Methods: Comprehensive expression analysis (Agilent 41K human genome oligo microarray) and DNA sequencing of the TP53 gene in 38 Japanese BC (30 Stage I-II, 8 stage III-IV; 20 TP53 wt, 20 TP53 mt) were performed using RNA and DNA obtained from the microdissected frozen tumor samples. We determined a gene set consisted of 33 genes from differentially expressed genes depending on the p53 status in the 26 BC (training set) and validated the ability to predict p53 status in the remaining 12 BC (test set). Prognostic value of the gene set was analyzed in 29 BC (stage I or II), and were validated using publicly available dataset of the independent 295 BC (stage I or II), van de Vijver et al. NEJM 2002). Results: The GEP using the 33 genes, many of which related in cell cycle and cell division, predicted the p53 status (wt or mt p53 signature) accurately in the test set (accuracy: 83%, overall accuracy: 95%). The p53 signature has the ability to predict RFS of the 29 early BC (Log Rank, P=0.032). It divided the 295 early BC into 176 wt and 119 mt group, and also has the ability to predict both RFS and OS (Log Rank, both P&lt;0.0001). This was also true when the cohort were stratified by ER status, LN status, St. Gallen criteria and NIH criteria, and retained the predicted value in ER+, LN+, LN-, St. Gallen (intermediate/high) and NIH (high) subgroups (Log Rank, P&lt;0.0001). Conclusions: The p53 signature is a powerful and independent predictor of the outcome of disease in early breast cancer than standard systems based on clinical and histologic criteria. No significant financial relationships to disclose.
Does smoking impair the quality of life of 34 year olds with alpha-1 antitrypsin deficiency?
Authors: Laura Cano Montero, Meltem Nystedt Düzakin, Eeva Piitulainen
Journal: European Respiratory Journal (2011)

Background:  Alpha 1-antitrypsin (AAT) protects lung tissue against degradation. Hereditary AAT deficiency increases the risk of pulmonary emphysema. During 1972-74 all newborns in Sweden where screened regarding AAT. Out of 200 000 newborns, 129 with severe (PiZZ) and 55 with moderate (PiSZ) deficiency were identified. We have examined whether smoking affects the quality of life in the cohort of individuals with AAT deficiency at the age of 34.   Method:  The study included 129 PiZZ and 55 PiSZ individuals, and 300 age matched PiMM controls with normal AAT level. The questionnaires on smoking habits and the St. George9s Respiratory Questionnaire (SGQR) where answered by the participants. Low scores indicate better quality of life in a 0-100 scale in the SGQR questionnaire.   Results:  104 PiZZ, 41 PiSZ individuals and 134 PiMM answered the SGRQ questionnaire. The mean total score in SGQR was 6.8 (SD 8.9) for PiZZ, 6.0 (SD 6.9) for PiSZ and 5.6 (SD 6.1) for PiMM (ns). The mean total score for all the 80 study participants who had ever smoked was 7.4 (SD 8.0) and 5.6 (SD 7.1) for all 199 non-smokers (p   Conclusion:  Smoking impairs the quality of life already at the age of 34 in the Swedish population. In smokers with alpha-1 antitrypsin deficiency the quality of life was also worse than in non-smokers, but the difference was not significant.
G0S2 Suppresses Oncogenic Transformation by Repressing a MYC-Regulated Transcriptional Program
Authors: Christina Y. Yim, David J. Sekula, Mary P. Hever-Jardine, Xi Liu, Joshua M. Warzecha, Janice Tam, Sarah J. Freemantle, Ethan Dmitrovsky, Michael J. Spinella
Journal: Cancer Research (2016)

Abstract Methylation-mediated silencing of G0–G1 switch gene 2 (G0S2) has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 opposes oncogene-induced transformation using G0s2-null immortalized mouse embryonic fibroblasts (MEF). G0s2-null MEFs were readily transformed with HRAS or EGFR treatment compared with wild-type MEFs. Importantly, restoration of G0S2 reversed HRAS-driven transformation. G0S2 is known to regulate fat metabolism by attenuating adipose triglyceride lipase (ATGL), but repression of oncogene-induced transformation by G0S2 was independent of ATGL inhibition. Gene expression analysis revealed an upregulation of gene signatures associated with transformation, proliferation, and MYC targets in G0s2-null MEFs. RNAi-mediated ablation and pharmacologic inhibition of MYC abrogated oncogene-induced transformation of G0s2-null MEFs. Furthermore, we found that G0S2 was highly expressed in normal breast tissues compared with malignant tissue. Intriguingly, high levels of G0S2 were also associated with a decrease in breast cancer recurrence rates, especially in estrogen receptor–positive subtypes, and overexpression of G0S2 repressed the proliferation of breast cancer cells in vitro. Taken together, these findings indicate that G0S2 functions as a tumor suppressor in part by opposing MYC activity, prompting further investigation of the mechanisms by which G0S2 silencing mediates MYC-induced oncogenesis in other malignancies. Cancer Res; 76(5); 1204–13. ©2016 AACR.
Effect of Busulfan on Oncornavirus-Like Activity in Platelets and Chromosomes in Polycythemia Vera and Essential Thrombocythemia 2
Authors: Isadore Brodsky, Anthony A. Fuscaldo, Barry J. Erlick, Kathryn E. Fuscaldo
Journal: JNCI Journal of the National Cancer Institute (1977)

The effect of busulfan therapy on the activity of oncornavirus-like particles and chromosome patterns in patients with polycythemia vera and essential thrombocythemia was studied. Three patients had pretreatment platelet counts greater than 1 million/µl, abnormal bone marrow karyotypes, and electron microscopic and biochemical evidence of oncornavirus. The results demonstrated that in all 3 patients virus-like particles and reverse transcriptase-like activity could no longer be found in the platelets within 2–4 weeks after the initiation of busulfan treatment. The platelet count was still elevated at this point for each patient, although the count returned to normal levels within 2–3 weeks after virus-like activity was no longer detectable. The chromosome patterns, characterized by aneuploidy (30–50%) before treatment, improved after therapy.
Susceptibility and Resistance to Friend Leukemia Virus: Effect on Production of Migration-Inhibition Factor23
Authors: Richard F. Mortensen, Walter S. Ceglowski, Herman Frledman
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Susceptibility and Resistance to Friend Leukemia Virus: Effect on Production of Migration-Inhibition Factor Get access Richard F. Mortensen, Richard F. Mortensen Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter S. Ceglowski, Walter S. Ceglowski Search for other works by this author on: Oxford Academic PubMed Google Scholar Herman Frledman Herman Frledman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 499–505, https://doi.org/10.1093/jnci/52.2.499 Published: 01 February 1974 Article history Received: 19 July 1973 Accepted: 17 October 1973 Published: 01 February 1974
Phase II study of sunitinib administered in a continuous daily dosing regimen in patients (pts) with advanced GIST
Authors: S. George, P. G. Casali, J. Blay, A. Le Cesne, A. R. Tyler, M. T. Quigley, V. Tassell, C. M. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2006)

9532 Background: Sunitinib malate (SU11248) is an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities due to inhibition of KIT, VEGFRs, PDGFRs, RET, and FLT3. In previous phase I/II and III trials in pts with imatinib-resistant GIST, sunitinib demonstrated efficacy and favorable clinical tolerability when administered in 6-week treatment cycles consisting of 4 weeks sunitinib (50 mg QD), followed by 2 weeks off treatment. The current study examined continuous sunitinib dosing as a way to avoid potential reactivation of tumor cells during the off-treatment period. Methods: This open-label, multicenter, phase II trial was designed to evaluate the efficacy, safety, and tolerability of sunitinib administered once daily using a continuous-treatment regimen in pts with imatinib-resistant GIST. Treatment is initiated with 37.5 mg sunitinib daily, with the option to titrate dosing on an individual basis depending on tolerability. The primary study endpoint is clinical benefit rate, defined as percent of evaluable pts with confirmed CR, PR, or SD ≥24 weeks using RECIST. Secondary endpoints included ORR, TTP, PFS, OS, and safety/tolerability measures. Results: Of 28 pts who had started treatment at the time of this analysis, early results were available for 17 pts from two centers. The most commonly occurring treatment-related adverse events were stomatitis, hand-foot syndrome, gastroesophageal reflex, and fatigue, which were generally grade 1. Two pts experienced treatment-related grade 3 hypertension, and another exhibited grade 3 asymptomatic neutropenia. Five pts have been evaluated for benefit after 8 weeks of treatment. Stable disease (which is the clinical benefit typically observed in GIST pts treated with sunitinib) was demonstrated in all five pts. Expanded safety/tolerability and efficacy results will be available for presentation. Conclusions: Continuous dosing of sunitinib is feasible and appears to be associated with acceptable tolerability in pts with imatinib-refractory GIST, similar to the extensive experience documented with intermittent sunitinib dosing. It is possible that continuous daily dosing of sunitinib may further improve the outcomes of pts with GIST. [Table: see text]
<i>MET</i> Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non–Small Cell Lung Carcinoma with Poor Prognosis
Authors: Joanna H. Tong, Sai F. Yeung, Anthony W.H. Chan, Lau Y. Chung, Shuk L. Chau, Raymond Wai Ming Lung, Carol Y. Tong, Chit Chow, Edith K.Y. Tin, Yau H. Yu, Hui Li, Yi Pan, Wing P. Chak, Calvin S.H. Ng, Tony S.K. Mok, Ka F. To
Journal: Clinical Cancer Research (2016)

Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naïve non-small cell lung carcinoma (NSCLC).Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METΔ14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively.METΔ14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METΔ14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METΔ14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio ≥5) was mutually exclusive to the major driver genes except METΔ14. Oncogenic METΔ14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METΔ14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METΔ14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis.The high incidence of METΔ14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients. Clin Cancer Res; 22(12); 3048-56. ©2016 AACRSee related commentary by Drilon, p. 2832.
Hemodynamic and hormonal changes during erythropoietin therapy in hemodialysis patients.
Authors: M Lebel, I Kingma, J H Grose, S Langlois
Journal: Journal of the American Society of Nephrology (1998)

To better understand the mechanism of recombinant human erythropoietin (rhEPO)-induced increase in BP, hemodynamic parameters, body fluid volumes, and the hormones implicated in BP regulation were studied in 32 anemic hemodialysis patients before and after 3 to 4 mo of rhEPO therapy. Hemoglobin levels increased from 83 +/- 1.5 to 119 +/- 2.3 g/L (P < 0.01) after rhEPO therapy (25 to 43 U/kg) administered subcutaneously three times weekly. Mean 24-h systolic and diastolic ambulatory BP were significantly increased by 14 +/- 3 and 10 +/- 2 mmHg, respectively (P < 0.01 for both groups). Systemic vascular resistance consistently increased by 28 +/- 5% (P < 0.01), whereas cardiac output was decreased by 6 +/- 3% (P < 0.05). Red blood cell mass increased by 510 +/- 35 ml (P < 0.01), whereas plasma volume decreased by 420 +/- 66 ml (P < 0.01), which resulted in a nonsignificant increase in total blood volume. Extracellular fluid volume and exchangeable sodium were decreased by 873 +/- 255 ml (P < 0.01) and 125 mmol (P < 0.01), respectively. There was a positive correlation between the changes in exchangeable sodium and in systolic BP (r = 0.41, P < 0.05). Furthermore, a greater increase in 24-h systolic BP was observed in patients in whom exchangeable sodium increased or remained unchanged (n = 10) compared with patients (n = 22) with decreased exchangeable sodium (20 +/- 4 mmHg versus 8 +/- 2 mmHg, respectively, P < 0.01). Plasma catecholamines, plasma renin concentration, plasma atrial natriuretic peptide, and plasma endothelin-1 did not significantly change with rhEPO treatment, whereas plasma aldosterone increased significantly (P < 0.01). Although volume-independent mechanisms may contribute to rhEPO-induced BP increase, the results presented here suggest the importance of optimally reducing extracellular fluid volume to prevent, at least in part, the development of hypertension often observed with improved uremic anemia in these patients.
Facilitating preventive behaviors among women undergoing BRCA1/2 Testing
Authors: S. M. Miller, P. Roussi, M. Rodoletz, M. Daly, K. Sherman, M. Diefenbach, A. Godwin
Journal: Journal of Clinical Oncology (2004)

1011 Background: Genetic testing for BRCA 1/2 provides complex, probabilistic information that can have far-reaching effects with regard to cancer prevention and screening behaviors. We evaluated an enhanced counseling intervention, designed to promote well-informed decision making for follow-up preventive options, among women at putative hereditary risk for breast/ovarian cancer. Methods: Participants (N=180; 96% Caucasian; mean age 47; 56% college educated; 57% unaffected breast/ovarian cancer) received standard group education, an individual pedigree review, a standard pre-disclosure session, and a disclosure session to receive test results. In addition, immediately following pedigree review, women were randomized to receive either: 1) an Enhanced Counseling session involving structured role-play to allow the participant to anticipate possible test outcomes and plan for post-result consequences; or 2) a General Health Information control session, to control for time and attention. Sociodemographic variables were assessed at baseline. Preventive and screening behaviors were assessed 6 months-post feedback of results. Results: As expected, the majority of women (98%) opted for genetic testing, with 86% receiving inconclusive/indeterminate, 11% positive and 3% negative test results for a BRCA1 or BRCA2 genetic mutation. Results of logistic regression analyses showed that women who received enhanced counseling were more likely to undergo prophylactic oophorectomy than control group women (p = .04). Further, the uptake of preventive surgery was greater for women with positive test results (p = .02) and less education (p = .04). Finally, women who received inconclusive/indeterminate results were less likely to undergo CA 125 testing (p = .04). Conclusions: These results suggest that uptake of preventive surgery is greater when participants are provided with the opportunity to fully process their risk-related options. In addition, specific genetic test result and level of education should be considered when designing BRCA1/2-related counseling interventions. No significant financial relationships to disclose.
Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).
Authors: S. Kempin, B. J. Lee, H. T. Thaler, B. Koziner, S. Hecht, T. Gee, Z. Arlin, C. Little, D. Straus, L. Reich, E. Phillips, Hamid Al-Mondhiry, M. Dowling, K. Mayer, B. Clarkson
Journal: Blood (1982)
Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.
Authors: Y Yamada, Y Hatta, K Murata, K Sugawara, S Ikeda, M Mine, T Maeda, Y Hirakata, S Kamihira, K Tsukasaki, S Ogawa, H Hirai, H P Koeffler, M Tomonaga
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the frequency of the deletions of p15/p16 genes in adult T-cell leukemia (ATL) cells and to evaluate their value in the diagnosis of clinical subtypes of ATL patients and the prediction of their clinical outcome. MATERIALS AND METHODS Peripheral-blood samples from 114 patients with ATL were examined by Southern blot analysis. In five chronic-type patients who showed disease progression to acute type, serial samples also were examined. RESULTS Among 114 patients, 28 (24.6%) showed the deletions of p15 and/or p16 genes. The results were well correlated with the clinical subtypes. Patients with deleted p15 and/or p16 genes had significantly shorter survival times than the patients in whom both genes were preserved (P &lt; .0001). A similar decline in survival time was observed in the analyses within the same subtypes. In multivariate analysis using the Cox proportional hazard model, the deletions of p15 and/or p16 genes emerged as an independent prognostic indicator. Moreover, three of the five chronic-type patients who progressed to acute type lost the p16 gene alone or both the p15 and p16 genes at their exacerbation phase. CONCLUSION The results suggest the following: (1) that the deletions of p15 and/or p16 genes play a key role in the progression of ATL; and (2) that these deletions are reliable prognostic factors that predict shortened survival times.
Long-term Marijuana Use and Cognitive Impairment in Middle Age
Authors: Wayne Hall, Michael Lynskey
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal