tbuckley/cabot-search huggingface dataset:
Changes With Age in the Hematopoietic System in a Cesarean-Derived, Barrier-Maintained Colony of Wistar Rats
Authors: Margaret M. F. Wagner
Journal: JNCI Journal of the National Cancer Institute (1976)

In a colony of cesarean-derived barrier-maintained inbred W rats given saline injections into the right pleural cavities, histologic and cytologic changes due to age were examined in the bone marrow, lymphatic tissue, and lungs; hematologic trends were also evaluated. The thymus showed two changes with age: 1) atrophy, which was evidenced by plasma cells near the blood vessels and among the cords of epithelial cells; and 2) disruption of the normal architecture of the gland. In all available thymuses, changes showed a transition toward malignancy. As the bone marrow showed increasing cellularity with time, polymorphonuclear cells and precursors appeared to increase. In lymph nodes, lymphocytes in the paracortical area were excessive and resembled the lymphocytes of the "lymphoid bursts" found in the thymus. In the lungs, small parabronchial and paravascular collections of mononuclear cells, occurring with slightly increasing frequency with age, were consistently found; however, any lung disease associated with these cells was not evident. In the blood, absolute numbers of mononuclear and polymorphonuclear cells were altered.
Search for Specificity in Natural Cell-Mediated Cytotoxicity<xref ref-type="fn" rid="FN2">2</xref>
Authors: M Takasugi, M Hardiwidjaja, R McAllister, M Peer
Journal: JNCI Journal of the National Cancer Institute (1979)

Differences in antigenicity between the human osteosarcoma cell line TE 85/B and its feline sarcoma virus-infected subline NIH E1041 were detected by competitive inhibition of natural cell-mediated cytotoxicity (NCMC). Whether the differences could be attributed to the viral infection was investigated by absorption and elution studies of antibodies that determine the specificlty of NCMC against the cell lines. Antibodies from the serum of healthy individuals were first absorbed onto target cells against which they were to be tested and then eluted to provide antibodies putatively specific for the target cells. Trypsin-treated effector cells were restored with the absorbed serum or eluted antibodies and tested against TE 85/B and its intentionally infected sublines. The differences observed previously between TE 85/B and NIH E1041 were extended to the detection of small differences in antigenicity among all sublines. Separately maintained sublines from the same culture became antigenically different with continuous passage. The causes for these specific changes were unknown, but a role for the control of these antigens by NCMC was suggested. Differences in antigenicity between virus-infected sublines cultured separately need not be related to the virus infection.
Aromatase inhibitor (AI) related musculoskeletal (MS) symptoms: Is preventing osteoporosis the key to eliminating these symptoms?
Authors: A. Muslimani, M. N. Iqbal, T. P. Spiro, A. A. Chaudhry, H. C. Taylor, H. A. Daw
Journal: Journal of Clinical Oncology (2008)

9554 Background: AI are increasingly being used as adjuvant endocrine therapy for breast cancer (BC). Patients (pts) receiving AI report a higher incidence of MS and bone fractures; the mechanism and risk factors for this correlation are not well studied. We correlate symptomatology with: bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis). Methods: We retrospectively reviewed charts of 856 hormone receptor-positive non-metastatic BC pts between Jan 1999 - Oct 2007. 316 pts met the inclusion criteria of treatment with an AI (anastrozole, letrozole, or exemestane) for at least 3 months and availability of a dual- energy x-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia (GBPM) ≥5/10 points on Visual Analog Pain Scale, bone fracture after beginning AI, any tamoxifen treatment and Ca/Bis therapy were recorded. Results: Table 1 shows a significant association between symptoms and DEXA-BMD results (p<0.001). The more severe the symptoms the greater the likelihood of osteopenia and osteoporosis. Similarly, the group receiving tamoxifen before AI had fewer pts with arthralgia or generalized bone pain/myalgia (GBPM) or bone fracture (p=<0.001) and had more pts with normal BMD (p<0.001). Furthermore, the group receiving AI plus Ca/Bis had more pts without MS symptoms and fewer fractures. Finally, the group receiving steroidal AI compared to non-steroidal AI had more pts with arthralgia or GBPM and bone fractures (p<0.001). Conclusions: Pts on AI who develop osteoporosis are at increased risk of MS symptoms and bone fracture. Co-medication with Ca/Bis reduces the likelihood for osteoporosis and MS symptoms. Pts who received tamoxifen before AI were less likely to develop AI-related MS symptoms. We recommend that pts on AI should be offered Ca/Bis to reduce the incidence of MS symptoms and fracture, especially if pts are receiving steroidal AI and/or did not receive tamoxifen prior to AI. Total Normal BMD Osteopenia (T<-1.5 SD) Osteoporosis (T<-2.5 SD) N N N No MS symptoms 143 92 37 14 Arthralgia + Generalized bone pain/myalgias 138 13 40 85 Clinical bone fracture 35 0 0 35 Mantel-Haenszel correlation test was used No significant financial relationships to disclose.
Large cell lymphomas of the stomach: improved prognosis with complete resection of all intrinsic gastrointestinal disease.
Authors: S Paulson, R G Sheehan, M J Stone, E P Frenkel
Journal: Journal of Clinical Oncology (1983)

Thirty-seven consecutive patients with large cell lymphoma involving the stomach were evaluated between 1974 and 1980. All seven stage IE patients underwent complete resection of the stomach and all patients are alive 21-41 mo after resection. Of 18 stage IIE, 11 underwent complete resection. Two resected patients without postoperative therapy died of their disease. Six patients treated with chemotherapy are alive and well, and two of three patients treated with radiotherapy remain alive without disease. Seven patients had incomplete resection or biopsy, and only one remains alive at 34 mo. Of eight stage IV patients, four had complete resection and chemotherapy without recurrence of their disease. All four patients who were not resected have died of their disease. This study strongly supports the role of early surgery in the management of gastric large cell lymphomas.
Obesity Does Not Affect the Recurrence Free Survival Rates in Children Less Than 20 Years of Age in Acute Promyelocytic Leukemia (APL)
Authors: Ji Heon (Paul) Lee, Alfred W. Rademaker, Bayard L. Powell, Susan Geyer, Richard A. Larson, John Gregory, Nobuko Hijiya, James H. Feusner
Journal: Blood (2014)
A novel cellular microarray identifies functional deficiencies in tumor-specific T cell responses
Authors: Y. Soen, D. S. Chen, T. B. Stuge, J. S. Weber, P. P. Lee, P. O. Brown, M. M. Davis
Journal: Journal of Clinical Oncology (2004)

2510 Background: Immune based therapies that evoke a T cell response against tumor-specific antigens is an attractive therapeutic approach. However, the ongoing development of such therapies, which include vaccines, immune modulators, dendritic cell therapy and adoptive immunotherapy, is hampered by difficulty in assessing the quantity, breadth and functional activity of the T cell response to a given treatment. Here, we describe a novel, high-throughput method to profile different populations of tumor-specific T cells for specific functional defects post-peptide vaccine therapy. Methods: Cellular microarrays comprised of printed peptide-MHC spots, co-printed with anti-cytokine antibodies and other factors, on a single microarray, were produced for the rapid capture of antigen-specific T cell populations and functional analysis in geographically distinct regions. Viable peripheral blood mononuclear cell samples taken from patients with malignant melanoma at different time points during ongoing peptide-vaccination protocols were analyzed on the microarray. Functionally active tumor-specific T cells secrete cytokines such as Interferon-γ, TNF-α, IL-2, or granzyme B, which are captured and detected next to the cell. Peptide-pulsed target cells may also be added to the captured T cells, and target cell killing ascertained. Results: The peptide-MHC/cytokine cellular microarray was capable of rapidly identifying several different peptide-specific T cell populations emerging following peptide-vaccination. However, tumor-specific T cells expressed a functionally defective profile, lacking the ability to specifically secrete certain cytokines, such as IFN-γ. Conclusions: This novel cellular microarray device is effective at rapidly identifying peptide-specific T cell populations simultaneously, and specifically determining their functional profile at a single cell resolution. This is essential to evaluating the response to immunotherapy protocols, and understanding the potential inadequacy of the generated immune response. No significant financial relationships to disclose.
Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney. 1976.
Authors: H Murer, U Hopfer, R Kinne
Journal: Journal of the American Society of Nephrology (1998)

Journal of the American Society of Nephrology : JASN 9(1):p 143-150, January 1998. | DOI: 10.1681/ASN.V91143
Abstract P072: Who Becomes Weak on Statins? Effect Modification Exposed in a RCT by Risk Factor Compounding
Authors: Beatrice A Golomb, Sabrina Koperski
Journal: Circulation (2013)

Background: Some patients develop muscle weakness ( MW ) on statins but MW has not been affirmed in RCTs. Existing evidence suggests muscle problems may arise more commonly in those who are older, female, have a history of muscle problems, or exercise more. We assessed whether statin effects on MW can be unmasked by attending to effect modification, assessing if pairing of known risk factors ( RFs ) may amplify and expose MW in subgroups. Method: In a double blind RCT, 1016 adults (68% men) without DM or CVD were randomized equally to simvastatin 20mg, pravastatin 40mg or placebo for 6 months. MW was rated at baseline (0-10) and as change from baseline (-2 to +2). T-tests of difference in self-rated change in MW compared placebo to each statin arm, examining hypothesized vulnerable subgroups based on a) paired age/sex vulnerability (female + age &gt;65); and paired weakness+exercise vulnerability (baseline weakness rated &gt;0, + regular exercise &gt;5x/week). Results: Statins vs placebo did not increase MW in the full sample. Trends were not significant in those with individual RFs. Statins significantly increased MW in both risk-factor pairings ( Table ). In older women, mean MW increase on statins rose as age advanced further, from 0.19 (age &gt;65) to 0.26 (&gt;70), 0.37 (&gt;75), and 1 (&gt;80), while MW on placebo remained unchanged or improved. Statins also increased MW in subjects with any baseline MW (rated &gt;0) who engaged in regular exercise: Effects were larger, but the subgroup smaller. Discussion: In subgroups suggested by coupling of RFs in existing literature, analysis identifies significantly increased MW with statins vs placebo, providing, to our knowledge, the first RCT evidence of MW on statins. Older women represent an important group in whom MW increased. In those with any baseline MW who exercise regularly (as may be recommended), MW worsened with statins. Findings were consistent across statin randomization arms. This may offer an approach to better unmask adverse effects in RCTs.
BNN27, a synthetic derivative of dehydroepiandrosterone, suppresses allergic airway disease
Authors: Maria Aggelakopoulou, Angeliki Malamou, Davina C.M. Simoes, Ioannis Charalampopoulos, Achille Gravanis, Vily Panoutsakopoulou
Journal: European Respiratory Journal (2012)

Neurosteroids comprise a family of endogenous steroid hormones mainly known for their role in neuronal development and survival. A member of this family, dehydroepiandrosterone (DHEA), exhibits anti-inflammatory effects. Although DHEA could be beneficial in allergy, long-term administration of this molecule may induce side-effects, as it metabolizes into other steroids such as androgens and estrogens. Thus, we tested the effects of a DHEA-synthetic-analog BNN27 that does not metabolize to steroids, on allergic airway inflammation and allergic immune responses.For this we used a well-established mouse model for allergic asthma. Our results demonstrate that administration of BNN27 significantly suppressed allergic disease and the immune responses that mediate it. This included suppressed airway hyperresponsiveness, decreased pulmonary eosinophilia, suppressed allergen-specific IL-4 and IL-13 production, as well as significantly decreased allergen–specific IgE. Moreover, allergic mice treated with BNN27 had increased numbers of CD3 +  CD4 + CD25 +  Foxp3 +  T regulatory cells and suppressive CD11c +  PDCA-1 +  plasmacytoid dendritic cells.We also found that BNN27 suppressed Th2 responses  in vitro . We conclude that administration of the synthetic neurosteroid BNN27 has a significant immunomodulatory effect and protects from allergic airway inflammation.
The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold
Authors: Cian O'Leary, Brenton Cavanagh, Ronald E. Unger, C. James Kirkpatrick, Shirley O'Dea, Fergal J. O'Brien, Sally-Ann Cryan
Journal: Biomaterials (2016)
A phase I/II study of weekly intraperitoneal (IP) paclitaxel (PAC) with monthly intravenous (IV) carboplatin (CBDCA) for optimal debulked epithelial ovarian cancer (EOC) with peritoneal disease (PED)
Authors: S. Takeuchi, Y. Terai, H. Yamaguchi, S. Yamabe, M. Ueda, M. Ueki, T. Maruo, T. Sugiyama
Journal: Journal of Clinical Oncology (2005)

5120 Background: Although taxane-platinum regimens improved the response rate (RR) in treatment of EOC, long survival has not been obtained due to uncontrollable PED. IP is thought to be one of the modality to control PED. Concerning weekly IP-PAC, the recommended dose (RD) was 60–65 mg/m2/weekly by GOG study (Francis, Markmann, et al. JCO,1995). Objectives: We conducted a phase I/II study of combination regimen with weekly IP-PAC and monthly IV-CBDCA to define the RD and toxicity profiles as well as the response using serum CA125 levels by the Rustin’s criteria. Methods: Eligible patients (pts) were the optimal debulked stage ≥IC with PED. Regimen consisted of IP-PAC, on days 1, 8, 15 at a starting dose level (DL)1: 45 mg/m2, DL2: 60 mg/m2, DL3: 75 mg/m2. CBDCA was administered monthly at fixed dose of AUC 5 on day 1 only. At least 2 courses were performed. Results: Nine pts (DL1: 3pts, DL2: 6pts) were enrolled according to a modified Fibonacci schedule. Ip-reservoir port was put in all pts. Pharmacokinetics of PAC at DL1: Peak plasma concentration was 63.0±18.5 ng/ml at 8 hrs and it decreased gradually and remained over 10.0±2.5 ng/ml in 96 hrs. No grade (G)3 adverse effects were observed at DL1. At DL2, two pts with G3 neutropenia out of 6 pts was observed. Concerning non-hematologic toxicities, one of G1-abdominal pain was observed at first course of DL2. After that the prophylactic NSAID on D1 to D4 was used in other 5 pts, the pain had not been observed. One G3- and one G1-hypersensitivity to CBDCA was observed. As for CA125-RR, 5CR+2PR+1SD/8 were obtained. The median time to progression was 382+ days. MTD had not been reached in this study but further DL3 trial was not performed in the ethical viewpoint, because satisfactory responses had been observed at DL2 which seemed to be the RD in the weekly IP-PAC study of Francis, et al. Conclusions: This combination therapy was feasible and might be effective at 60 mg/m2 IP-PAC with AUC 5 IV-CBDCA. Further phase III setting study using this regimen will be conducted. No significant financial relationships to disclose.
Primary resistances to EGFR inhibitors (EGFRi) in HPV-positive and -negative oropharyngeal squamous cell carcinoma (OSCC).
Authors: F. Perrone, B. Cortelazzi, M. Orsenigo, G. Jocollè, E. Tarantino, S. Brich, P. Bossi, L. Locati, L. F. Licitra, S. Pilotti
Journal: Journal of Clinical Oncology (2010)

10591 Background: HPV-positive and negative OSCC, despite a common EGFR expression, have a distinct biology and clinical behaviour, thus we hypothesize different mechanisms of primary resistance to EGFRi. Methods: PI3KCA, PTEN, HER2 and IGF-1R status was investigated in 17 HPV16-positive and 57 HPV16-negative fixed untreated OSCCs through FISH, sequencing, cDNA relative quantification by means of real-time PCR (method 2-ΔΔCt) and immunohistochemistry. Results: PI3KCA gene amplification involved only HPV16-negative (13%) cases, while a gain of PI3KCA gene copy number similarly occurred in HPV16-positive (29%) and negative (25%) OSCC. Activating mutations play a marginal role both in HPV16-positive (6%) and negative (2%) OSCC. An higher occurrence of PI3KCA transcript values, 31 folds > than the lower one, was found in HPV16-positive (60%) compared with negative (27%) OSCC (p=0.05). PTEN gene loss was restricted to HPV16-positive (12%) cases, while PTEN mutation similarly involved both HPV16-positive (9%) and negative (10%) OSSC. Overall, PI3KCA and PTEN alterations was more frequent in HPV16- positive (70%) than negative (44%) OSCC. Despite a statistically significant higher occurrence of an increased HER2 gene/chromosome 17 copy number in HPV16-negative (46%) than positive (18%) OSSC (p<0.004), no case showed HER2 expression. IGF-1R cytogenetic analysis revealed a statistically significant higher frequency of increased IGF- 1R/chromosome 15 copy number in HPV16-negative (41%) than positive (7%) OSCC (p=0.02). This is in keeping with the higher occurrence of IGF-1R transcript values, 30 folds > than the lower one, detected in HPV16-negative (73%) than positive (15%) cases (p<0.001). Most OSCC showed expression of the cognate ligands IGF1 and IGF2, however HPV16-negative cases expressed higher IGF1 levels than HPV16-positive OSCC. Conclusions: PI3KCA/PTEN alterations could be responsible to primary EGFRi resistance particularly in HPV16-positive tumors, while IGF-1R could be associated with resistance mainly in HPV16-negative OSCC. HER2 seems not to be involved. Based on our results, resistances to EGFRi should be tackled differently according to HPV tumor status. No significant financial relationships to disclose.
Randomized phase II trial of infusional fluorouracil, epirubicin, and cyclophosphamide versus infusional fluorouracil, epirubicin, and cisplatin in patients with advanced breast cancer.
Authors: T Eisen, I E Smith, S Johnston, P A Ellis, J Prendiville, M T Seymour, G Walsh, S Ashley
Journal: Journal of Clinical Oncology (1998)

PURPOSE We previously developed an inpatient regimen that consisted of infusional fluorouracil (5-FU), epirubicin, and cisplatin (ECisF), with a response rate of 86% in advanced breast cancer. The current phase II 2:1 randomized study investigated whether cyclophosphamide can be substituted for cisplatin (ECycloF) to reduce toxicity and allow the regimen to be administered on an outpatient basis without loss of efficacy. PATIENTS AND METHODS Ninety-six women (median age, 49 years; range, 28 to 73) with breast cancer (59 metastatic, 37 locally advanced) received continuous infusional 5-FU (200 mg/m2/d via Hickman line) and six cycles of epirubicin (60 mg/m2 every 21 days) with either cyclophosphamide 600 mg/m2 every 21 days (38 metastatic, 24 locally advanced) or cisplatin 60 mg/m2 every 21 days (21 metastatic, 13 locally advanced). There were no significant differences in patient characteristics between these groups. RESULTS ECycloF was better tolerated than ECisF in terms of lethargy (P = .005), stomatitis (P = .008), plantar palmar erythema (P = .02), constipation (P &lt; .001), thrombosis (P = .0014), and nausea and vomiting (P = .05). Although there was a trend toward more anemia and leukopenia with ECisF (P =. 1), there was no significant difference in the rates of infection. Efficacy was comparable in terms of overall response (69% v 68%), complete response (CR; 13% v 15%), and median progression-free survival (9 v 8 months). CONCLUSION ECycloF is an outpatient regimen with a lower incidence of severe nonhematologic toxicity than inpatient ECisF; it has comparable efficacy and is considerably more economical.
Fluorouracil+interferon alfa+ interleukin-2 chemoimmunotherapy in metastatic renal cell cancer patients
Authors: O. Er, M. Ozkan, M. Altinbas, S. H. Coskun, B. Eser, F. Altuntas, M. Cetin, A. Unal
Journal: Journal of Clinical Oncology (2004)

4682 Background: Metastatic renal cell cancer (MRCC) shows atypical clinical behavior and is resistant to chemotherapy, so effective treatment is difficult. The response rate of cytotoxic chemotherapy is around 5–10%. Immunotherapy might result in additional benefit. There are studies showing different results about effect of nephrectomy on survival. The purpose of this study was to determine the efficacy of chemoimmunotherapy (CIT) in MRCC patients followed at Erciyes University Medical Oncology clinic. Methods:The patients with histopathologically confirmed MRCC received a combination of Fluorouracil 400mg/m2 intravenously once a week, and alternatively Interferon alfa (IFN) 10MU 3 days a week and Interleukin-2 18MU 3 days a week subcutaneously. Results:We enrolled into the study 23 MRCC patients whose performance status was ECOG 0–2. The median age was 60 years (range 40–72) and 19 patients were male, 4 female. Twenty patients were evaluable. Nephrectomy was performed on 12 patients. Nine patients had palliative radiotherapy to metastatic regions. All patients but one had CIT as first line treatment. CIT was administered median 10 weeks (range 2–32). Partial remission was obtained in 2 patients, stable disease in 5 and progression in 13, no complete response was detected. Median overall survival (OAS) was calculated as 10±2.3 (95%CI 5.5–14.5) months, progression free survival (PFS) 7±1.0 (95%CI 5.1–8.9) months. One year OAS and PFS rate was 27% and 7%, respectively.Median OAS for patients with and without nephrectomy was 10±1.4 (95%CI 7.2–12.8) and 5±3.4 (95%CI 0.0–11.7) months, median PFS 7±1.5 months (95%CI 4.1–9.9) and 4±2.1 months (95%CI 0.0–8.2) respectively and there was no statistically significant difference (p=0.27 and p=0.20). Five patients were alive at time of analysis. Most common complaints were fatigue, fever and nausea. Grade 3–4 side effect was not observed. Conclusions: This chemoimmunotherapy scheme seems to be moderately effective and has mild side effect profile. No significant financial relationships to disclose.