tbuckley/cabot-search huggingface dataset:
High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.
Authors: H M Lazarus, P Crilley, N Ciobanu, R J Creger, R M Fox, D C Shina, S I Bulova, R Gucalp, B W Cooper, D Topolsky
Journal: Journal of Clinical Oncology (1992)

We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease.Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites.Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion.This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).
Bone marrow microenvironment (ME) associated genes identified prior to all altered 48 hours after bortexomib test-dose application and prognosis of multiple myeloma (MM) treated with total therapy 3 (TT3)
Authors: P. Qu, J. Haessler, B. Barlogie, J. Shaughnessy
Journal: Journal of Clinical Oncology (2009)

8520 Background: Total Therapy 3 (TT3) incorporated bortezomib (BOR) to co-target ME that plays an important role in MM progression and drug resistance. Consenting patients received a BOR test dose of 1mg/m2 to determine whether ME alterations induced 48hr post-BOR could clarify the drug's in-vivo mechanism of action in the context of achieving MM control. Methods: Bone marrow biopsies were obtained at baseline (BL) prior to and 48hr after BOR (PB) in 70 of 303 patients receiving TT3a (training set) and in 45 of 177 patients enrolled in TT3b (test set). Among 608 ME genes distinguishing BL and PB training samples, 58 were identified as being significantly linked to short event-free survival (EFS). A summary score was computed based on the percent change of these 58 genes (PB-ME-S). Additionally, 20 ME genes were selected whose BL expression predicted OS, arriving at a BL score (BL-ME-S). Results: Applying the PB-ME-S score, 3-yr OS and EFS estimates were 96% and 96% among the 49 patients with low PB-ME-S and 50% and 38% in the 21 with high PB-ME-S (both p&lt;0.0001). Follow-up is too short to validate the PB-ME-S model in the test set of 45 patients in TT3b. The BL-ME-S distinguished OS and EFS in the training set of 70 patients, with 3-yr OS and EFS estimates of 92% and 91% among the 50 patients with low and 54% and 45% in the 20 patients with high BL-ME-S (both P&lt;0.0001). These data were validated in 113 patients with only BL-ME data: 3-yr OS and EFS were 90% and 85% among the 89 patients with low as opposed to 70% and 55% among the 14 patients with high BL-ME-S (p=0.001, p=0.002). TT3 survival was independently significantly affected by PB-ME-S (OS: HR=12.74, p=0.002; EFS: HR=14.32, p&lt;0.001) and BL-ME-S (EFS: HR=3.10, p=0.045), whereas the univariately significant role of BL-PC-S for both endpoints could not be confirmed on multivariate analysis. Conclusions: To our knowledge, this is the first report documenting a validated prognostic role of ME for cancer survival. Key genes shared by both PB-ME-S and BL-ME-S models are involved in endothelial and mesenchymal stem-cell signaling, the details of which will be reported at the meeting. [Table: see text]
Treatment of anemia with epoetin alfa 80,000 U QW in cancer patients receiving chemotherapy
Authors: G. Tarabay, P. Braly, J. J. Baker, D. Williams, R. J. Waltzman
Journal: Journal of Clinical Oncology (2004)

8205 Background: The efficacy of epoetin alfa 40,000 U subcutaneously (SC) once weekly (QW) for the treatment of chemotherapy (CT)-induced anemia in cancer patients (pts) has been demonstrated in clinical studies. Based on pilot studies, we hypothesized that higher initiation doses may result in more timely hematologic response (HR) and a higher HR rate when historically compared to the standard dose of 40,000 U SC QW. Methods: This ongoing, nonrandomized, open-label, pilot study is investigating HR and safety of epoetin alfa 80,000 U SC QW for up to 12 weeks (wks) in anemic (Hb ≤11 g/dL) pts with nonmyeloid malignancies undergoing CT. Primary end points are HR rates (minor: Hb increase ≥1–<2 g/dL from baseline [BL]; major: Hb increase ≥2 g/dL from BL), based on number of pts evaluable for a given week and independent of transfusion within 28 days. Results: 16 of a target of 60 pts (50% women; mean age 63 years; 88% ECOG PS 0–1; BL Hb 9.8 ± 0.7 g/d) have ≥1 post-BL assessment and are included in this analysis. Overall HR rates were 70% and 88% after 4 and 8 wks, respectively (Table). Mean times to 1 g/dL and 2 g/dL Hb increases were 3.9 ± 3.5 wks (n = 11) and 4.8 ± 2.9 wks (n = 8), respectively. Dose was reduced to 60,000 U SC QW in 8 pts and subsequently to 40,000 U SC QW in 3 pts due to Hb increase >1.3-g/dL in 2-wk period (n = 9), Hb >13 g/dL (n = 1), and physician decision (n = 1). Mean time to first dose reduction was 4.0 ± 2.0 wks (n = 8). 6 pts had ≥1 dose held (5 due to Hb >13 g/dL and 1 due to adverse event [AE]). AEs of any grade were reported in 5 pts, none related to study drug. The most common AE was diarrhea (5/40). Two pts had serious AEs (1 neutropenic fever/thrombocytopenia; 1 death from pulmonary embolism). There were no clinically significant changes in blood pressure. Conclusions: These preliminary data suggest that higher initiation doses of epoetin alfa may result in a shorter time to ≥ 2g/dL Hb increase than historically seen with 40,000 U QW. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Johnson & Johnson Johnson & Johnson Johnson & Johnson Ortho Biotech Products, LP
Chromosome Studies During Long-Term Cultivation of Epithelioid Cercopithecus and Cynomolgus Monkey Kidney Cell Lines
Authors: J FERGUSON, G A TOMKINS
Journal: JNCI Journal of the National Cancer Institute (1964)

Cytogenetic studies were performed on epithelioid cells derived from Cercopithecus monkey kidneys and cynomolgus monkey embryo kidneys. The cells were grown in tissue culture for periods of up to 22 months during which, in some instances, more than 130 passages were made. Chromosome counts were performed at intervals, and increases in chromosome number were observed in all lines surviving for more than 50 to 60 passages. The diploid chromosome number was replaced with a range of chromosome numbers in the triploid region. Some changes were noted in chromosome morphology, but the chromosomes could still be clearly identified as belonging to the species of origin of the cell line. While these chromosomal changes were taking place, the cell cultures showed no apparent change in morphology or growth rate. There was no appreciable difference in the behavior of lines derived from kidneys of the two different monkey species. Epithelioid cell lines were of particular interest because of their widespread use for in vitro virus and biochemical studies and because of the implication of these cells as contaminants in the reported establishment of some cell lines.
Altered Carbohydrate Content of Alpha&lt;sub&gt;1&lt;/sub&gt;-Antitrypsin in Patients With Cancer
Authors: I Rostenberg, J Guízar-Vázquez, R Peñaloza
Journal: JNCI Journal of the National Cancer Institute (1978)

The glycosylation of IgG and alpha1-antitrypsin (alpha1-AT) was studied by their precipitation with concanavalin A in a codified serum panel from the National Cancer Institute (Bethesda, Md.) and the Mayo Clinic (Rochester, Minn.). The serum panel was composed of samples from 98 patients with cancer of the lung, prostate gland, or gastrointestinal tract, 50 samples from patients with benign inflammatory diseases from the same organs as those of the cancer patients, and 41 samples from apparently healthy smokers. The assay for alpha1-AT revealed statistically significant differences in levels between the patients with cancer, the patients with benign diseases, and the smokers. However, tests revealed no statistically significant difference in IgG levels among the three groups. These results suggest that cancer may alter the glycosylation of alpha1-AT. The possibility remains that the test for alpha1-AT can detect genetic differences among individuals, but studies of families are needed before a final conclusion can be made.
Abstract 10115: Decreased Renal Function Associated With More Appropriate ICD Shocks and a Higher Mortality
Authors: M S Buiten, A C van der Heijden, J I Rotmans, J W Jukema, M J Schalij, L van Erven
Journal: Circulation (2013)

Introduction: Patients with chronic kidney disease represent a special group within ICD recipients. Sudden Cardiac Death (SCD) is an important cause of death in these patients, but they also suffer...
Effect of Nintedanib (Bibf 1120) Combined with Standard 2Nd-Line Docetaxel in Nsclc Patients Who Received Prior Pemetrexed in Lume-Lung 1: a Randomised, Placebo-Controlled Phase III Trial
Authors: A. Mellemgaard, S. Orlov, M. Krzakowski, J. von Pawel, M. Gottfried, I. Bondarenko, J. Barrueco, H. Buchner, J. Hocke, R. Kaiser, S. Novello, J. Douillard, M. Reck
Journal: Annals of Oncology (2014)
A multicenter phase I study of cabazitaxel (Cbz), mitoxantrone (Mito), and prednisone (Pred) (CAMP) for chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rahul Raj Aggarwal, Vivian K. Weinberg, Charles J. Ryan, Andrea Harzstark, Alan H. Bryce, Christina Louise Derleth, Kimberly Lowe, Eric Jay Small
Journal: Journal of Clinical Oncology (2014)

243 Background: Cbz/pred extends survival in mCRPC patients (pts) following docetaxel and first-line studies comparing Cbz to docetaxel are ongoing. Mito/pred also has anti-tumor activity in mCRPC and a non-overlapping mechanism of action and toxicity profile with Cbz. A multicenter phase I trial was initiated through the DOD PCCTC to establish the maximally tolerated dose (MTD) of the combination of Cbz, Mito, and Pred. Methods: Chemotherapy (chemo)-naive pts with mCRPC were enrolled in an accelerated titration design. The primary objective was to determine the MTD of CAMP; secondary objectives included assessing PSA and objective response rates and duration of response. Starting dose of Cbz was 25 mg/m 2 (the currently approved single-agent dose) and Mito 4 mg/m 2 , administered on day 1 of a 21-day cycle. Mito was escalated by 2 mg/m 2 per dose level. Pred 5 mg BID and pegfilgrastim were administered with each cycle. Results: 9 pts were enrolled (dose level I, N = 1; dose level II, N = 1; dose level III, N = 3; dose level IV N = 4). The median age was 67 (range 55-81) and the median baseline PSA was 82.3 (range 20.4-791.2). There were 2 DLTs observed at dose level IV (Cbz 25 mg/m 2 + mito 10 mg/m 2 ), both grade 4 sepsis. The most common grade 3 adverse events were hematologic (neutropenia, n = 5; febrile neutropenia, n = 2, thrombocytopenia, n = 2). 6 of 9 pts remain on study (range 2.2 - 10.5+ months). Maximal PSA declines from baseline &gt; 50% have been observed in 4/7 (57%) evaluable pts to date. 2 of 4 pts with measurable disease have experienced partial responses and a third has had a minor response after 4 cycles of chemo. The median progression-free survival and duration of response have not been reached. Conclusions: The approved single-agent dosage of Mito (12 mg/m 2 ) could not be safely reached in combination with Cbz 25 mg/m 2 . Pre-planned evaluation of an alternate dosing strategy combining Mito with Cbz 20 mg/m 2 , which has demonstrated activity in mCRPC and potentially less hematologic toxicity, is underway. Preliminary efficacy data are encouraging but additional follow-up and further study of the treatment combination is required. Clinical trial information: NCT01594918.
C19-Steroid Metabolism by Spontaneous Adenocarcinoma of the A × C Rat Ventral Prostate2
Authors: Sydney A. Shain, Wayne M. Nitchuk, Bruce McCullough
Journal: JNCI Journal of the National Cancer Institute (1977)

Specimens of ventral prostate from 37- to 46-month-old Andradurin-treated A X C rats demonstrated three primary morphologic patterns, each being divisible into two sub-groups based upon the extent of glandular alteration. The principal groups were: group 1, hyperplasia; group 2, atypical hyperplasia; and group 3, adenocarcinoma. The secondary classifications were: subgroup (+), few glands involved; and subgroup (++), most glands involved. Multiple parameters of ventral prostate testosterone metabolic potential failed to distinguish the morphologically diverse prostate specimens of groups (1+). 1(++), 2(+), 2(++), and 3(+) which predominantly metabolized testosterone to 5alpha-reduced 17beta-hydroxysteroids. By contrast, testosterone metabolism by ventral prostate specimens predominantly composed of neoplastic epithelium, group 3(++), was distinct from all other prostate specimens. The distinguishing feature was a shift to more prominent elaboration of 17-ketosteroids, principally delta4-androstenedione, and a cteroids. The change in this biochemical parameter of prostate epithelial cell function was indicated to be an early manifestation of the neoplastic transformation.
Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales.
Authors: S R Palumbi, C S Baker
Journal: Molecular Biology and Evolution (1994)

Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.
HMPS (2-hydroxy-4-methoxyphenylstilbene), a stilbene derivative of rhapontigenin, and cell death by mitochondrial apoptotic pathway in breast cancer cells
Authors: J. Jung, H. Park, H. Jung, Y. Eun, J. Kim, Y. Chae, J. Yang, Y. Lee, S. E. Aiyar, R. J. Santen, S. Kim
Journal: Journal of Clinical Oncology (2009)

e22130 Background: Breast cancer with resistance to clinical therapy is a significant threat to live of recurrent breast cancer patients, and chemo-resistant breast cancer is increasing rapidly. During last several decades, natural stilbenoids have been studied on anticancer effects in vitro and in vivo, and resveratrol is the most famous stilbene as a leading compound in the studies of anticancer compounds derived from plants. HMPS (2-hydroxy-4-methoxyphenylstilbene) is an analogue derived from rhapontigenin (3,5,3'-trihydroxy-4'-methoxy-trans-stilbene), which is a stilbene of herbal plant Rheum undulatum. TMS (2,3',4,5'-tetramethoxystilbene), an another stilbene analogue from rhapontigenin, was reported potent anticancer effect on tamoxifen-resistant MCF-7 cells. In this study we investigated inhibitory effect of HMPS on proliferation of breast cancer and a potential for a new therapeutic candidate. Methods: We examined cell viability of MCF-7 and MDA-MB-231 by MTT assay after exposure to various concentrations of HMPS. Apoptotic cell death induced by HMPS was investigated by florescence microscopy, cell cycle analysis and western blotting. Results: Cell viability of breast cancer cells after 24 h exposure to HMPS decreased significantly, and both ER-positive and ER-negative breast cancer cells responded to HMPS. HMPS induced nucleus fragmentation and G2/M arrest followed by sub-G1 accumulation of apoptotic cells in time- and dose-dependent manner. During the process of cell death induced by HMPS, mitochondrial membrane potential was disturbed and caspase-3 and PARP cleavage were observed. Moreover, HMPS decreased cell number of LTED MCF-7 cells(Long term estradiol deprived cell) effectively. Conclusions: Our results demonstrates that proliferation inhibitory effect of HMPS is about 50-fold more potent than those of rhapontigenin and furthermore HMPS also inhibits cell growth of LTED cells which are difficult to treat therapeutic agents. Therefore, HMPS may be a potential therapeutic candidate to treat the recurrent breast cancer by alone or combination with other conventional anticancer agents. No significant financial relationships to disclose.
Effect of 1-β-D-Arabinofuranosylcytosine on Cell Cycle Passage Time&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Karon, S Shirakawa
Journal: JNCI Journal of the National Cancer Institute (1970)

1-beta-D-Arabinofuranosylcytosine (ara-C) affects the passage rate of cells from S to G2 phase to a greater extent than from G1 to S. This finding is consistent with the fact that the compound may have its major biological effect during the latter part of S and the early part of G2. The magnitude of these effects is related to the dose and duration of ara-C administration. Inhibition of DNA synthesis can occur without disturbances in transit time.
A prospective study of residual-disease monitoring of theALL1/AF4 transcript in patients with t(4;11) acute lymphoblastic leukemia
Authors: Giuseppe Cimino, Loredana Elia, Maria Cristina Rapanotti, Teresa Sprovieri, Marco Mancini, Antonio Cuneo, Cristina Mecucci, Giuseppe Fioritoni, Mario Carotenuto, Enrica Morra, Vincenzo Liso, Luciana Annino, Giuseppe Saglio, Giulio De Rossi, Robin Foà, Franco Mandelli
Journal: Blood (2000)
Predicting patterns of failure in esophageal cancer following tri-modality therapy: Why histology matters
Authors: M. Koshy, R. Battafarano, W. Burrows, M. Krasna, B. Greenwald, H. Mannuel, M. Suntharalingam
Journal: Journal of Clinical Oncology (2008)

4553 Background: This analysis was performed to determine the impact of histology on pathologic complete response (pCR) and failure patterns for patients with esophageal cancer undergoing neo-adjuvant chemo-radiation followed by surgical resection. Methods: Between 1992–2006, 164 pts. underwent tri-modality therapy for esophageal cancer. The median RT dose was 50.4Gy. Pts. received Cisplatin/5-Fluorouracil for 2 cycles during RT. Pts. were taken to surgery at a median of 7 weeks. Overall survival (OS), disease free survival (DFS), and loco-regional control (LRC) were calculated using the Kaplan-Meir product method. Results: The median follow-up was 18 months and 27 months in surviving pts. There were 68% with adenocarcinoma (AC) and 32% with squamous cell (SCC). A pCR rate was seen in 41.4%. PCR was achieved in 35% with AC and 54% with SCC (p - 0.01). Forty one percent died due to recurrent disease. Of the failures, 66% were distant, 21% were loco-regional, 9% were loco-regional and distant, and 3% were found to have progressed at the time of resection. Of the distant failures, the first site of failure was the liver in 40%, the lungs in 16%, the bones in 20%, and the para-aortic nodes in 4%. Of the AC’s with recurrence, 39% failed locally, and 68% failed distantly. Of the SCC with recurrence, there were no local failures and 100% failed distantly (p-.001). The three year LRC for AC and SCC was 71% and 100% (p=0.03). On multivariate analysis histology predicted for pCR and improved LRC (p=0.001). The median OS and DFS was 27 months and 20 months. Median OS and DFS of AC with a pCR versus no pCR was 70 months and 59 months versus 26 months and 13 months (p=0.01). Median OS and DFS of SCC with a pCR versus no pCR was 44 months and 41 months versus 18 months and 14 months (p=0.33). Conclusions: This data reveals that esophageal cancer outcomes are predicted by histology. AC’s with complete pathologic response have excellent long term disease free outcomes. Although, SCC is associated with a higher rate of pCR, it is not associated with significantly improved disease free outcomes. Furthermore, SCC’s have a higher likelihood for developing distant metastasis and are at a relatively low risk of failing loco-regionally. This data highlights the need for improved systemic control in this subgroup of patients. No significant financial relationships to disclose.
Host immune deficiency in immune complex nephritis.
Authors: B S Ooi, D J Cohen
Journal: Journal of the American Society of Nephrology (1995)

Evidence is reviewed that indicates that an immune deficiency state may underlie patients with immune complex nephritis. Studies in several laboratories provide data that show defective immune function in patients with nephritis at the following loci: defective immunoglobulin production, impaired monocyte Fc and C3b receptor function, diminished complement biosynthesis, and decreased mesangial cell colony-stimulating factor-1 biosynthesis. Aberrant monocyte function may be an important common denominator. The validation of this hypothesis has important implications for therapeutic strategies.
One in seven colorectal cancer patients is under 50, US study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

<b>Background:</b> Mutations of the filamin A locus (<i>FLNA</i>) on Xq28 have been established in girls with periventricular nodular heterotopia and in patients with otopalatodigital and overlapping phenotypes, the pathogenesis of these phenotypes being thought to be quite distinct. To date only six male cases of periventricular nodular heterotopia (PVNH) have been reported and these almost invariably associated with severe neurological signs. <b>Methods and Results:</b> We report a new phenotype of male PVNH, with relatively normal development, no epilepsy or other neurological abnormality, severe constipation, and facial dysmorphism and without a discernible skeletal phenotype. This phenotype is associated with a splice site mutation in <i>FLNA</i> c.1923C&gt;T, resulting in the generation of both normal and aberrant mRNA. <b>Conclusions:</b> We postulate that the patient retains enough FLNA function to avoid the usual lethality associated with loss of function mutations in males and suggest that the severe constipation may be a clue to the molecular aetiology of other X linked conditions associated with severe constipation.