tbuckley/cabot-search huggingface dataset:
Mixed type endometrial carcinoma: Clinicopathologic comparison between two large academic institutions.
Authors: S. Bandyopadhyay, S. Sethi, D. Schultz, A. R. GABA, M. A. Elshaikh, A. Munkarah, B. Albashiti, R. Ali-Fehmi
Journal: Journal of Clinical Oncology (2010)

e15559 Background: The diagnosis of endometrioid carcinomas, mixed type, is based upon presence of a serous component varying from 10% to 25%. This range may introduce variation and subjectivity in classifying these tumors by different pathologists. In our study we reviewed cases of endometrial carcinoma, mixed type from two large academic institutions (hospital A and B) and analyzed the impact of this diagnosis on clinical pathologic variables and patients' survival. Methods: The pathology databases of both hospitals were queried for the period 1998 - 2005 to retrieve all cases classified as endometrial carcinoma, mixed type. Gynecologic pathologists and general surgical pathologists at the respective insititutions reviewed all cases. Patient information regarding race, age and survival were obtained from the medical charts. Chi square testing was used to compare the clinicopathologic variables between the groups. Kaplan Meier survival analysis and log rank were used to assess survival. Results: A total of 73 patients with a diagnosis of endometrial cancer, mixed type were included in the study based on the review of the slides and reports (36 from Hospital A and 37 from Hospital B).There was no significant differences between these 2 groups with respect to incidence of angiolymphatic invasion, depth of myometrial invasion, lymph node status and tumor stage. Although the overall survival did not show a statistically significant difference, there was a trend for longer survival in patients from Hospital B (median: 141.8 months) compared to those from hospital A (median: 51.4 months; p = 0.321). The age at presentation was significantly different between the 2 groups with Hospital A having a larger population of patients less than 60 years (p = 0.038). Conclusions: Despite the variation in the cut offs used for diagnosis of mixed endometrial cancer, there was no difference in the 2 groups of mixed endometrial cancers evaluated. The difference in the survival outcomes may reflect the significant impact of the difference in proprotions of serous carcinoma. his needs to be addressed in a largere study taking types of treatment into consideration difference. No significant financial relationships to disclose.
DNA Damage and Repair Pathway Profiles as Biomarkers in High-Risk Prostate Cancer
Authors: Sean E. McGuire
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Addition of gabapentin (G) to a modified FOLFOX regimen does not reduce neurotoxicity in patients (pts) with advanced colorectal cancer (CRC)
Authors: P. Mitchell, D. Goldstein, M. Michael, P. Beale, M. Friedlander, J. Zalcberg, S. Clarke, S. White
Journal: Journal of Clinical Oncology (2005)

3581 Background: In order to determine the neuroprotectant effect of G against oxaliplatin-induced neurotoxicity, we sequentially recruited pt cohorts in a non-randomised phase II trial to FOLFOX then FOLFOX+G. Inclusion criteria were: advanced CRC; chemonaive except adjuvant completed ≥ 6 mths; measurable disease; PS 0–2. Pts received on D1 oxaliplatin 100mg/m2 IV over 2 hrs, LV 20mg/m2 bolus, 5-FU 400mg/m2 bolus then 5FU 2.4g/m2 46-hour infusion. Cycles were 2-wkly until PD or unacceptable toxicity. In addition, G cohort pts received G 300mg/d po, increased as required by 300mg/d increments (max 1800mg). Over 2 yrs, 40 pts were recruited to FOLFOX then 41 to FOLFOX+G. Minimum f/up was 18 mths. All but one pt received at least one dose of oxaliplatin and were evaluable for toxicity and treatment delivery. Pt characteristics were well balanced between cohorts. Maximum doses of G were 300mg/d in 10 pts, 600mg/d in 15, 900mg/d in 4, 1200mg/d in 9, and 1800mg/d in 3 pts. Treatment delivery for FOLFOX and FOLFOX+G cohorts respectively: median cycles 10 (1–13) vs 9 (1–12); oxaliplatin dose reduction >10% in 55% vs 50% of pts; cycles delayed >2days 19% vs 14%; treatment cessation due to toxicity 36% vs 37% (NS). RDI for FOLFOX and FOLFOX+G was oxaliplatin 82% vs 87%; 5FU bolus 52% vs 69%; 5FU infusion 82% vs 87% (NS). Responses (CR+PR) were seen in 48% of pts in each cohort. There were no significant difference in non-neurological toxicity.There was no significant difference in severity of neurotoxicity. For pts with grade 2/3 neurotoxicity, median time to recovery to grade 0/1 was 3.3mths for FOLFOX and 0.5mths for FOLFOX+G, however persistence of grade 2/3 neurotoxicity at 1 yr was 0% vs 17% respectively (NS). Conclusions: Addition of G to FOLFOX does not improve ability to deliver protocol-specified treatment and does not significantly reduce either severity or duration of neurotoxicity. This trial was sponsored by Sanofi-Synthelabo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Sanofi Sanofi Sanofi
Safety and efficacy of adding rituximab to the ICE regimen (ifosfamide, carboplatin, and etoposide) in previously treated non-Hodgkin's lymphoma
Authors: D. C. Case, K. Ebrahim, M. Boyd, F. R. Aronson, D. M. Hayes
Journal: Journal of Clinical Oncology (2004)

6674 Background: Rituximab has been utilized as a single agent in previously treated non-Hodgkin's lymphoma. More recently Rituximab has been combined with other agents such as CHOP. Previously we have utilized ICE in relapsing /refractory lymphoma. For the last three years, we have combined rituximab with ICE to assess safety and efficacy. Methods: In the prior series, patients received ifosfamide 600 mg/m2 IV qd x3, carboplatin 250 mg/m2 IV day, and etoposide 100 mg/m2 IV cont'd infusion qd x3 along with mesna 20% of the ifosfamide dose IV 3x/d for 3 days. Treatment was given every 28 days for 1–6 cycles pending response. In the current series Rituximab was given at 375 mg/m2 IV two days before each cycle. Results: In the prior series, 31 patients were treated with ICE. Thirteen patients (42%) responded with 10 PR (2–6 months) and 3 CR (6–24 months). Myelosuppression was the dose-limiting toxicity with med ANC 800/mm2 during the first cycle. In the current series, 17 patients have been treated with R-ICE. All patients were able to tolerate the addition of Rituximab. Myelosuppression was comparable in the present series related to ICE and was the dose-limiting toxicity. Of the patients treated with R-ICE to date, 10 (58%) have responded: 5 PR (3–6 months) and 5 CR (6+-24+ months). The ages (median 62 years) and amount of prior treatment (median 3 prior regimens) were comparable. Conclusions: Rituximab can be safely added to the ICE regimen in previously treated patients with lymphoma and may improve the response rate. No significant financial relationships to disclose.
Abstract 9728: Arterial Stiffness is Associated with Carotid Atheromatosis in Hypertensive Patients (Campania Salute Network)
Authors: Giuseppina Casalnuovo, Eva Gerdts, Raffaele Izzo, Marina De Marco, Renata Giudice, Giovanni De Simone, Bruno Trimarco, Nicola De Luca
Journal: Circulation (2011)

Background: Pulse pressure/stroke index (PP/SVi) is a validated measure of total arterial stiffness, but its relation to carotid atherosclerosis is unknown. Methods: Data from 6209 hypertensive patients without prevalent cardiovascular disease (coronary heart disease, stroke, heart failure) in the Campania Salute Network underwent standard transthoracic echocardiography and carotid ultrasound. SVi was obtained by echocardiographic LV volumes computation; mean and maximal (max) carotid intima-media thickness (IMT) and the presence of plaques (≥1.3 mm) in the common and internal carotid arteries were assessed. The population was stratified into thirtiles of PP/SVi and analyzed using ANOVA. Results: Increase from the lowest to the highest thirtiles of PP/SVi was associated with increasing age, progressively higher systolic and diastolic blood pressure (BP), higher total cholesterol and larger number of antihypertensive drugs (Table 1). The highest PP/SVi thirtile was also associated with higher max and mean IMT and higher prevalence of carotid plaques (Table1). In multivariate logistic regression analysis, compared to the lowest thirtiles, the prevalence of carotid plaque increased by 16% (95% confidence interval [CI] 1-34%, p&lt;0.05) in the second PPSVi thirtile and by 33% (95% [CI] 15-55%, p&lt;0.01) in the the highest PPSVi thirtile, independently of significant associations with diabetes mellitus, age, gender and total cholesterol. Conclusion: In treated hypertensive patients included in the CampaniaSalute Network, higher PP/SVi is associated with carotid atherosclerosis independently of others confounders.
RADIOIMMUNOASSAY OF ERYTHROPOIETIN CIRCULATING LEVELS IN NORMAL AND POLYCYTHEMIC HUMAN BEINGS
Authors: Joseph F. Garcia, Shirley N. Ebbe, Lester Hollander, Hunter O. Cutting, Marilyn E. Miller, Eugene P. Cronkite
Journal: Journal of Clinical Investigation (1980)

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initialmore » practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less
Rituximab-supplemented high-dose sequential chemotherapy (R-HDS) has better EFS and PFS than R-CHOP in poor risk follicular lymphoma (FL) at diagnosis: A multicenter randomized GITMO/IIL trial
Authors: M. Ladetto, F. Benedetti, U. Vitolo, C. Patti, A. Rambaldi, A. Liberati, M. Musso, A. Pulsoni, A. M. Gianni, C. Tarella
Journal: Journal of Clinical Oncology (2006)

7525 Background: HDS with ASCT is effective and feasible in FL at the multicenter level and suitable for Rituximab supplementation (R-HDS). This randomized trial compared R-HDS with Rituximab-supplemented CHOP (R-CHOP) in poor risk FL patients (pts) &lt;60 yrs. Methods: Between 2000 and 2005, 136 pts have been randomized (68/arm). Eligibility required age-adjusted IPI ≥2 (125 pts) or, in the absence of this criterion, ≥3 IIL adverse factors (11 pts). Primary endpoint was EFS. Clinical features were: median age 50 yrs (22–60), stage III-IV 98%, elevated LDH 78%, bulky disease 66%, B symptoms 47%, extranodal disease (other than BM) 45%, ECOG PS &gt;1 47%. R-HDS consisted of: i. 2 APO and 2 DHAP; ii. sequential administration of Etoposide 2g/sqm, 2 Rituximab, Cyclophosphamide 7 g/sqm with PBPC collection (in vivo-purged with 2 additional Rituximab); iii. Mitoxantrone (60 mg/sqm) + L-Pam (180 mg/sqm) followed by 5–8 × 106 CD34+ cells/kg. R-CHOP consisted of 6 CHOP courses followed by 4–6 doses of Rituximab. Cross-over was allowed. bcl-2/I gH-based minimal residual disease analysis was planned. Assessement was “intention to treat”-based. Results: Current data are updated at 31/5/05. Next closing date will be April 2006. The two arms were balanced. 68% patients concluded R-CHOP (failures were due to progression 29% and toxicity 3%) and 78% R-HDS (failures due to progression 9%, toxicity 5%, poor mobilization/refusal 8%). Toxic deaths were 4 (2 in each arm); in addition 1 gastric cancer and 1 AML occurred in the R-HDS arm. Progressions and non-responses were 31% with R-CHOP and 11% with R-HDS (p &lt; 0.05) CRs were 58% and 87% respectively. Current median follow-up is 24 months. EFS and PFS at 24 months are 41% and 48% for R-CHOP and 66% and 75% for R-HDS (p &lt; .001). At present OS is similar. Salvage treatment following R-CHOP is currently known in 22 pts: 16 received R-HDS, with 10 achieving CR. Molecular remission, (two PCR-neg BM samples at 6 months intervals), was observed in 54% of R-CHOP and 77% of R-HDS pts Conclusions: R-HDS induces more CRs and has better EFS and PFS than R-CHOP in this rare and aggressive population of high-risk FL patients. These results cannot be extrapolated to standard-risk pts. [Table: see text]
Treatment of patients with metastatic solid tumors with intentionally mismatched lymphocytes activated with rIL-2 in the outpatient setting
Authors: R. Or, A. Ackerstein, S. Morecki, Y. Gelfand, S. Samuel, S. Slavin
Journal: Journal of Clinical Oncology (2004)

2576 Background: Graft vs malignancy (GVM) effects are well established in hematological malignancies with potential clinical application for metastatic solid tumors. We evaluated feasibility immunotherapy using intentionally mismatched lymphocytes in patients with resistant metastases. Methods: 21 patients with metastates, 12 males, 9 females, 1.5 - 74 (median 52) years old participated: breast (7); colon (4); glioblastoma (3); thyroid (1) ovary (1); multiple myeloma (2) and non-Hodgkin's lymphoma (1); melanoma (1), carcinoid (1). To improve efficacy and prolong duration of circulating donor lymphocytes, aiming for self-limited GVM effects, 10/21 patients received fludarabine 25mg/m2/day (x5) and Roferon A 3x106 IU/day (x2). On day 0, lymphocytes from mismatched family members were infused after in vitro activation (rIL-2 6,000 IU/mx4 days). In 5 patients with liver metastasis, lymphocytes were injected into the hepatic artery. Median mononuclear cell dose infused 1.4 (range 2–25.5) x 107/Kg. Starting with cell infusion (day 0), outpatient rIL-2 (6x106 IU/m2 daily) was self-administered 5 days, subcutaneously. Panorex was given in conjunction with cell therapy to 3 patients with metastatic colon cancer aiming for antibody-dependent cell-mediated cytotoxicity. Results: Treatment was well tolerated and no patient required admission. One with colon cancer had PR with transient engraftment of donor cells, showed no evidence of disease no chemotherapy for 16 months. Second patient with metastatic breast cancer developed skin rash compatible with cutaneous GVHD with liver enzyme abnormality. Albeit lack of evidence for chimerism, she had no evidence of progressive disease for 23 months. Two patients with multiple myeloma with no evidence of disease for 57,42 months respectively. The other 17 patients had progressed. Conclusions: Based on our observations in mice and man, adoptive immunotherapy with transient “parking” of mismatched, hence maximally activatable donor lymphocytes, is a feasible and well tolerated clinical tool, potentially useful for controlling minimal residual disease. No significant financial relationships to disclose.
A novel thiazole antibiotic compound selectively kills breast cancer cells through the inhibition of Forkhead Box M1 expression
Authors: Jimmy Kwok, Eric Lam
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3280 

The transcription factor forkhead box M1 (FoxM1) is an important master cell cycle regulator gene. FoxM1 controls the expression of many downstream targets involved in apoptosis, angiogenesis, metastasis, proliferation and the G2/M checkpoint. Primary breast cancer tumours and several other cancer cells often express elevated levels of FoxM1, whereas FoxM1 expression is undetectable in terminally differentiated cells. Therefore, it makes FoxM1 an attractive molecular candidate for targeted therapeutics. In this study, a member of the thiazole antibiotics family has been identified as a novel anti-tumour agent. The thiazole compound specifically down regulates FoxM1 protein expression in breast cancer cell lines in a dose-dependant manner in western blot analysis. However, the expression of FoxO3a, a closely related forkhead family member was not inhibited. RT-qPCR also showed a down-regulation of FoxM1 mRNA level in the presence of the thiazole compound over a 24 hour time period. Varying lengths of FoxM1 promoter, ApaI (0.3kb), HindIII (1.4 kb), PvuI (0.3 kB), Trident (2.4 kb) and FoxO3A promoter (1.5kb) were transfected separately into MCF-7 cells. Following thiazole drug treatment, luciferase assays showed that the thiazole compound inhibited the FoxM1 promoters transcriptional activity specifically, whereas the FoxO3a expression was not affected. A construct containing FoxM1 gene fused into CMV promoter was also transfected into COS-1 cells. FoxM1 was over-expressed in COS-1 cells under the regulation of CMV promoter, but both FoxM1 protein and mRNA expression was not inhibited in the presence of the thiazole compound. Thus, confirming that the thiazole compound specifically inhibits the FoxM1 promoter activity. The thiazole compound also inhibited in vitro invasiveness of MDA-MD-231 cells by reducing soft agar colony formation by up to 30%. Furthermore, the thiazole compound also completely inhibited cell migration of MCF-7 cells in the wound healing assay. Importantly, the thiazole compound also selectively activated apoptosis via both caspase 8 and caspase 9 induction in several breast cancer cell lines including MCF-7, BT474, SKBR-3, MDA-MB-231, T47D and ZR-75-1, but not in the normal breast epithelial cell line MCF-10A. FACS and BrdU analysis showed that the thiazole compound reduces the number of active S-phase cells, followed by a G2/M arrest before inducing apoptosis in MCF-7 cells. Critically, the thiazole compound had no effect on the cell cycle of MCF-10A. In conclusion, the thiazole compound selectively induced apoptosis in breast cancer cells through the inhibition of FoxM1 expression. Mice studies are been carried out to determine its effectiveness under in vivo models.
Serum lactate dehydrogenase (LDH) level as a prognostic factor for the patients with advanced gastric cancer
Authors: H. Lee, Y. Yuh, S. Kim
Journal: Journal of Clinical Oncology (2009)

e15621 Background: Though serum LDH level is frequently elevated in the patients with advanced gastric cancer, its clinical significance is still elusive. Moreover, the relationship between the change of serum LDH level after chemotherapy and the response to the treatment has not been studied, yet. We analyzed serum LDH level as a prognostic factor for the patients with advanced stomach cancer. Methods: We assessed serum LDH level before chemotherapy for the patients who were planned to receive palliative chemotherapy. We re-assessed their serum LDH level at the time when the response to chemotherapy was evaluated after 2–4 cycles of treatment. The survival duration and the response to chemotherapy for the patients with low serum LDH level were compared to the survival duration and the response to chemotherapy for the patients with high serum LDH level. The relationship between the change of serum LDH level and the response to the treatment was evaluated, too. Results: Total 118 patients were entered into this study and 114 patients were evaluable for their response to chemotherapy. Pre-treatment serum LDH level was normal in 88 patients and elevated in 30 patients. The response rate in the patients with high serum LDH level was significantly higher than the response rate in the patients with normal serum LDH level (34.5% versus 15.3%, p &lt; 0.05). However, the patients with normal serum LDH level lived longer than the patients with high serum LDH level (median: 378 days versus 206 days, p &lt; 0.001). The normalizing of the elevated serum LDH level after chemotherapy was related to the good response to treatment (response rate 50.0% versus 18.8%, p &lt; 0.05). Conclusions: For the patients with advanced gastric cancer, high serum LDH level was related to better response to chemotherapy but shorter survival duration. The normalization of elevated serum LDH level after chemotherapy was related to good response to treatment. No significant financial relationships to disclose.
Interobserverer variability of lobular neoplasia
Authors: Y. Choi, M. Pinto, L. Hao, A. Riba
Journal: Journal of Clinical Oncology (2005)

734 Background: Lobular neoplasia(LN) is presumed to have a distinct biological and phenotypical tumor characteristics, and clinical implication different from ductal neoplasia(DN). The histological diagnoses of either DN or LN or both can be problematic in those tumors with low grade morphological features.The interpretation can vary among pathologists. E-cadherin has shown to be useful in distinguishing DN or LN on the basis of complete membrane stain. In this pilot study, the accuracy and variability of histomorphological interpretation of LN was studied by using E-cadherin expression as a gold standard. Methods: Forty seven cases of breast lesions previously diagnosed as LN during the period of 1998 to 2002 were randomly selected from the departmental files in a 400 bed community hospital. Four surgical pathologists reviewed the slides in a blinded manner for the histopathologic interpretation. E-cadherin stain was conducted on the paraffin-embedded sections of the breast lesions using E-cadherin antibodies (prediluted, Cell Marque, Hot Springs, AK) and DAKO automated immunostainer after antigen retrieval with appropriate positive and negative controls. Only complete E-cadherin membrane reactivity of epithelial cells was recorded as positive.Incomplete membrane stain was considered as aberrant and absent staining as negative. Benign breast ducts used as positive internal control. Results: The histologic diagnoses of LN was confirmed by E-Cadherin stain in 76.5%(36/47) of the cases: of these 36 cases, 27 were diagnosed as LN on routine H&E stain by two or three pathologists and 9 were by one pathologist. E-cadherin stain changed the diagnoses of LN to DN in 12.7%(6/47), DN to LN in 6.3%(3/47) and DN to mixed LN/DN in 4.2% (2/47). E-cadherin membrane immunoreacivity appears to be heterogenous and does not always show complete absent membrane staining. Conclusions: The study confirms variability in interpreting LN on routine H&E stain among pathologists, and E-cadherin stain is useful in classifying LN versus DN. As an accurate interpretation of LN is essential for the management of LN, the standardization of E-Cadherin antibodies and interpretation appears to be eminent No significant financial relationships to disclose.