tbuckley/cabot-search huggingface dataset:
Tryptophan Metabolism in Patients With Bladder Cancer: Geographical Differences&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R R Brown, J M Price, G H Friedell, S W Burney
Journal: JNCI Journal of the National Cancer Institute (1969)

Abnormal levels of urinary tryptophan metabolites, after a loading dose of tryptophan, were more frequent in bladder cancer cases from Wisconsin than in those from the Boston area. The tryptophan metabolism of patients from the Boston area was more similar to that of previously studied patients with industrial bladder cancer than to that of patients from Wisconsin with spontaneous bladder cancer. These differences did not seem to be due to variations in vitamin B6 nutrition or other factors known to affect tryptophan metabolism. They may indicate other etiologic factors in the more urbanized Boston environment.
Clinical outcomes of adjuvant treatments for invasive thymoma: Dose chemotherapy influence prognosis?
Authors: S. Jeong, B. Cho, J. Jung, C. Im, Y. Kim, H. Choi, M. Park, S. Kim, K. Chung, J. Kim
Journal: Journal of Clinical Oncology (2007)

7715 Background: The aim of this study was to evaluate therapeutic outcomes and to validate prognostic factors, including adjuvant chemotherapy, in resected thymoma patients who received adjuvant treatment. Methods: One hundred thymoma patients who received post-surgical adjuvant therapy from 1995 to 2005 were retrospectively reviewed. 55 patients received only radiotherapy for the adjuvant therapy, while 45 patients received both radiotherapy and chemotherapy. The total radiation dose was 45–63 Gy, with a median dose of 50.4 Gy. The chemotherapy consisted of 6 cycles of doxorubicin, cisplatin, vincristine, and cyclophosphamide. Treatments were applied every 3–4 weeks. The median follow-up duration was 65 months (range, 5–200 months). Results: The 5-year overall survival (OS) and disease- free survival (DFS) rates were 75.7% (89.2% in stage II, 67.9% in stage III, and 52.1% in stage IV A ) and 70.3% (83% in stage II, 62.4% in stage III, and 33.6% in stage IV A ) respectively. According to multivariate analysis, the prognostic factors for OS were age, WHO histology, Masaoka stage, and recurrence, while pleural involvement and WHO histology had statistically significant impacts on DFS. Higher radiation dosage, positive resection margins, and adjuvant chemotherapy did not influence survival outcomes. The most common relapse site was the pleura (15 patients, 53.6%). The toxicity from chemotherapy and radiotherapy was manageable, with no deaths due to toxicity. Conclusion: The prognosis of invasive thymoma was poor despite adjuvant treatments with radiotherapy and chemotherapy. In addition to WHO histology, pleural involvement was the most important prognostic factor for recurrence. The pleura was the most common relapse site. Therefore, new modalities to reduce pleural recurrence are warranted. No significant financial relationships to disclose.
A multicenter phase II study of irinotecan in combination with G17DT immunogen in subjects with metastatic colorectal adenocarcinoma (CRC) refractory to previous irinotecan-based chemotherapy
Authors: C. M. Rocha Lima, R. Buck, K. Meyer, I. Mitrica, W. Perkins, D. Michaeli
Journal: Journal of Clinical Oncology (2004)

3573 Background: G17DT is a novel immunogen that raises antibodies to the growth factor gastrin-17 (G17). The purpose of this study was to determine the safety and efficacy of G17DT in combination with irinotecan in metastatic CRC subjects refractory to previous treatment with irinotecan-based chemotherapy and to correlate this with anti-G17 immune response. Methods: The study was an open-label, multinational, phase II trial in subjects with intact organ function, KPS≥70, and measurable disease. Subjects received irinotecan 125 mg/m2/90 min wk 5–8 q42 days. 500 μg G17DT was administered I.M. wk 1, 5, 9 with a booster at wk 26. Results: 158 subjects received G17DT, with 98 evaluable for tumor response. Best overall response was: CR (0%), 3 PR (3%), 32 SD (33%), and 63 PD (64%). Median survival was 219 days. 103 (69%) of subjects evaluable for antibody titers were immune responders (i.e., had at least one anti-G17 antibody titer ≥1 ELISA unit). Non-whites (95%) were more likely to be immune responders than whites (64%). Mean peak titer was 47.2 +/- 133.4; median peak titer was 3.7 U. Cox regression analysis showed anti-G17 immune response to be a predictor of survival (median survival in immune responders was 273 days) which remained statistically significant after adjusting for KPS (p <0.0001). There was no difference in sex, age, location of metastasis(es), and number of organ systems with metastasis(es) between the populations of anti-G17 responders and non-responders (when comparing baseline characteristics). Toxicity was consistent with irinotecan (diarrhea, nausea, anemia, vomiting, fatigue, anorexia, and neutropenia) except for injection site reactions (pain, induration, erythema, edema, and two abscesses) attributed to G17DT. Conclusion: The combination of G17DT with irinotecan results in an acceptable anti-G17 immune response, which correlated with promising survival in CRC subjects previously treated with irinotecan. Additional studies with G17DT in combination with chemotherapy for CRC are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aphton Corp. Pfizer Pfizer Aphton Coporation
Serum levels of sestrin 2 in patients with sarcoidosis
Authors: Aneza Roussou, Andriana Papaioannou, Effrosyni Manali, Aris Spathis, Nikoletta Pianou, Alexandros Georgakopoulos, John Tomos, Anna Karakatsani, Kostantinos Kostikas, Sofia Chatziioannou, Petros Karakitsos, Spyros Papiris
Journal: European Respiratory Journal (2014)

Introduction:Oxidative stress is involved in pathogenesis of Sarcoidosis. Sestrins are proteins with antioxidative capacity that accumulate in cells exposed to oxidative stress. The aim of our study was to test whether serum sestrin 2 (Ses2) levels in patients with sarcoidosis are related to disease extent, to the involvement of specific organs and to treatment with corticosteroids  Methods:Serum samples were collected from consecutive patients with sarcoidosis. Patients underwent pulmonary function tests, chest X-ray, HRCT and Positron Emission Tomography (PET). Patients with involvement of 3 or more organs were considered to have extended disease. Serum Ses2 levels were measured with ELISA  Results:35 patients (22 female) (mean age 54.0±14.4 years) were included in the study. Serum Se2 levels were higher in patients with limited disease compared to patients with extended disease [median(IQR) 3.19(1.61, 7.72) vs 0.89(0.68, 2.66)ng/mL, respectively p=0.009. Steroid naive patients with limited disease had higher serum Ses2 levels compared to those with extended disease [3.27(1.62, 18.19) vs 0.94(0.81, 2.17) respectively, p=0.024]. However, serum Ses2 levels were not related to disease extend in patients receiving corticosteroids [3.39(1.14, 6.16) vs 0.79(0.53, 5.09) for limited and extended disease respectively p=0.159]. Serum Ses2 levels were higher in patients with no node involvement compared to patients with any node involvement [4.96(1.63, 18.19) vs 1.88(0.88, 3.19) respectively p=0.036]  Conclusion:Serum Ses2 levels are lower in patients with extended sarcoidosis and those with node involvement. Corticosteroids seem to affect serum Ses2 levels. The possible antioxidative role of Ses2 in sarcoidosis has to be further evaluated.
Phase I and pharmacokinetic study of KRN8602 alone and with filgrastim in patients with advanced cancer.
Authors: K Clarke, R L Basser, D Maher, D J Morgan, J Cebon, R M Fox, J S Hill, C Alt, J Bartlett, H Geldard, A H Kaye, M D Green
Journal: Journal of Clinical Oncology (1998)

To determine the recommended dose, toxicity profile, and pharmacokinetics of KRN8602 (MX2-hydrochloride), a novel morpholino anthracycline with potent cytotoxicity against anthracycline-sensitive and resistant experimental tumors in vitro and in vivo.KRN8602 was administered alone in increasing doses to patients with advanced cancer or high-grade gliomas until dose-limiting toxicity (DLT) was observed in three or more of five patients treated in a dose level. Because neutropenia was dose limiting, further escalation was investigated with filgrastim support.Fifty-six assessable patients completed at least one cycle of chemotherapy. The recommended dose of KRN8602 alone was 40 mg/m2. Dose escalation was limited by neutropenia. The recommended dose of KRN8602 with filgrastim was 70 mg/m2, and limiting toxicities were neutropenia, diarrhea, and vomiting. The most commonly experienced nonhematologic toxicity was nausea and vomiting. Alopecia and mucositis were infrequent and mild. Pharmacokinetic parameters showed substantial variation, although the area under the plasma concentration-time curve (AUC) and maximum concentration both increased with dose. There was no relationship between pharmacokinetic parameters and toxicity.KRN8602 at doses of 40 mg/m2 when administered alone and 70 mg/m2 when administered with filgrastim appeared to be manageable. The major DLTs were neutropenia and, at higher doses, diarrhea and vomiting. The efficacy of this drug is currently being tested in phase II studies.
Expression of Carbohydrate Antigen 19-9 and Stage-Specific Embryonic Antigen 1 in Nontumorous and Tumorous Epithelia of the Human Colon and Rectum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Gong, S Hirohashi, Y Shimosato, M Watanabe, Y Ino, S Teshima, S Kodaira
Journal: JNCI Journal of the National Cancer Institute (1985)

The expression of carbohydrate antigen 19-9 (CA 19-9) and stage-specific embryonic antigen 1 (SSEA-1) in various human colorectal epithelia was examined by an immunohistochemical method. In mucosa remote from the carcinoma, CA 19-9 was not expressed, whereas SSEA-1 was only faintly expressed in lower crypts in all cases. In mucosa adjacent to the carcinoma, CA 19-9 was weakly expressed in upper crypts in 20% of the cases, whereas SSEA-1 was expressed not only in lower crypts in all cases but also in upper crypts in 93.3% of the cases. In adenoma, CA 19-9 was expressed in 80.6% of the cases, and SSEA-1 was expressed in all cases. The expression of both antigens was to some extent related to the degree of cellular atypia. In focal carcinoma in adenoma, CA 19-9 was strongly and diffusely expressed in 50% of the cases, and SSEA-1 was strongly and diffusely expressed in all cases. In advanced carcinoma, CA 19-9 was homogeneously or heterogeneously expressed in 82.2% of the cases, and SSEA-1 was homogeneously or heterogeneously expressed in all cases, but lower intensity of SSEA-1 staining was associated with a decrease in the degree of carcinoma differentiation. These results show that the expression of both CA 19-9 and SSEA-1 changes along with neoplastic transformation and progression in the colon and rectum. Immunohistochemical studies of SSEA-1 in flat colorectal mucosa might be a useful approach for detecting foci with preneoplastic change in the general population, whereas those of SSEA-1 and CA 19-9 could be a useful method for detecting focal carcinoma in adenoma.
Relationship between hot flashes and fatigue in men receiving hormonal therapy for prostate cancer
Authors: S. G. Patterson, E. M. Winters, P. B. Jacobsen
Journal: Journal of Clinical Oncology (2005)

8151 Background: Hormonal deprivation therapy is the recommended treatment option for the subset of prostate cancer patients considered to be “biochemical failures.” These men are often asymptomatic and do not show signs of metastatic disease, yet experience a progressive rise in PSA. Often these men are treated with hormonal deprivation. Use of hormonal deprivation therapy is associated with a number of side effects, including hot flashes. Very little is known about how these hot flashes affect men undergoing this form of treatment. Methods: Participants were asked to report fatigue with a fatigue symptom inventory and to report on the presence and severity of hot flashes. Patients were evaluated prior to the initiation of LHRH agonist and three months after initiation of LHRH agonist. We evaluated 39 men with prostate cancer (mean age = 68 years; range 42 - 89) who started LHRH agonist therapy. Sixty-one percent of these men received leuprolide (Lupron or Eligard), while the remainder received goserelin (Zoladex). Results: Seventy percent of the participants experienced hot flashes within the two weeks prior to follow-up assessment. In terms of severity, 24% of men with hot flashes described them as mild, 27% described them as moderate, 16% were severe, and 3% reported very severe hot flashes. Within this two-week period, the average number of hot flashes reported was 22 (SD = 20; range 1–77). Men reporting more severe hot flashes also reported higher levels of fatigue at the time of assessment (r = 0.38, p < .05). More severe hot flashes were also associated with greater average levels of fatigue (r = 0.34, p < .05) and a longer duration of fatigue (r = 0.38, p< .05). Conclusions: These results suggest a relationship between hot flashes and fatigue. More research is needed to determine the directionality of this association and to explore potential causal mechanisms. Larger sample sizes and a longitudinal design are necessary to elucidate this finding. No significant financial relationships to disclose.
Multiwalled Carbon Nanotubes Inhibit Tumor Progression in a Mouse Model
Authors: Lorena García‐Hevia, Juan C. Villegas, Fidel Fernández, Íñigo Casafont, Jesús González, Rafael Valiente, Mónica L. Fanarraga
Journal: Advanced Healthcare Materials (2016)

Understanding the molecular mechanisms underlying the biosynthetic interactions between particular nanomaterials with specific cells or proteins opens new alternatives in nanomedicine and nanotoxicology. Multiwalled carbon nanotubes (MWCNTs) have long been explored as drug delivery systems and nanomedicines against cancer. There are high expectations for their use in therapy and diagnosis. These filaments can translocate inside cultured cells and intermingle with the protein nanofilaments of the cytoskeleton, interfering with the biomechanics of cell division mimicking the effect of traditional microtubule‐binding anti‐cancer drugs such as paclitaxel. Here, it is shown how MWCNTs can trigger significant anti‐tumoral effects in vivo, in solid malignant melanomas produced by allograft transplantation. Interestingly, the MWCNT anti‐tumoral effects are maintained even in solid melanomas generated from paclitaxel‐resistant cells. These findings provide great expectation in the development of groundbreaking adjuvant synthetic microtubule‐stabilizing chemotherapies to overcome drug resistance in cancer.
Aluminum uptake and toxicity in cultured mouse hepatocytes.
Authors: K Abreo, J Jangula, S K Jain, M Sella, J Glass
Journal: Journal of the American Society of Nephrology (1991)

Hepatic aluminum (Al) accumulation in association with hepatobiliary dysfunction has been described in children receiving contaminated parenteral alimentation solutions and in aluminum-overloaded experimental animals. The mechanisms of hepatic Al uptake are not clearly understood, and it is not known whether Al is directly toxic to the hepatic cell or if toxicity occurs from the effect of Al on hepatic iron (Fe) metabolism. Al causes a microcytic hypochromic anemia and concomitant hepatic Al and Fe can accumulate in dialysis patients, suggesting that Al may alter Fe metabolism. Therefore, Al uptake and toxicity were studied in mouse hepatocytes in culture. Al accumulation, cell growth, media hepatic enzyme concentrations, and cell malonyldialdehyde concentrations, a marker of membrane lipid peroxidation, were measured in mouse hepatocytes grown in media containing either Al citrate, transferrin-Al (Tf-Al), or no additions over 96 h. Al uptake occurred only in cells grown in Tf-Al and Al citrate at 24 h and increased linearly achieving cellular concentrations at 96 h of 522 +/- 36 and 186 +/- 12 micrograms/L, respectively, compared with 31 +/- 3 micrograms/L (P less than 0.001) in control media. Inhibition of cell growth occurred at 48, 72, and 96 h (P less than 0.001), and media lactate dehydrogenase and aspartate aminotransferase concentrations increased starting at 48 and 72 h, respectively (P less than 0.001), only in media containing Tf-Al. Cell malonyldialdehyde levels were significantly higher in Tf-Al-loaded mouse hepatocytes compared with control cells at 96 h (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Female genital mutilation -- a form of child abuse [editorial]
Authors: Schroeder P
Journal: New England Journal of Medicine (1994)

Some immigrants have brought the practice of female genital mutilation to the United States. Representative Patricia Schroeder introduced a bill H.R. 3247 in Congress to prohibit genital mutilation and to provide education to immigrant communities. There are a number of practices that immigrants are required to leave at home such as polygamy and slavery. The courts have ruled that parents cannot endanger the lives or physical and mental well-being of their children to raise them within the confines of their own culture. Essentially the courts have balanced the right of parents to raise their children as they see fit and the states interest in the welfare of the children. In a 1944 Supreme Court case Prince v. Massachusetts a Jehovahs Witness was charged with violating the child-labor laws of Massachusetts by allowing her 9-year-old niece to sell religious pamphlets on the street. Even though the court supported parental rights in Wisconsin v. Yoder in 1972 the decision further defined when the government can intervene to protect a child. The Amish successfully argued that their tradition of removing their children from school was inseparably intertwined with their faith. Although the federal government and most states exempt faith healing in their child-abuse laws it is clear that a court can intervene if a child is threatened with death or serious and irreparable bodily injury from a medically curable condition. The Supreme Court did affirm a federal district courts decision to mandate lifesaving blood transfusions for children whose parents were Jehovahs Witnesses. Female genital mutilation is not required by any religious doctrine it irreparably cripples a girls sexuality and produces long-term health risks. All children must be protected equally regardless of where their parents are from and what customs they practiced in their native countries.
Acute effect of hookah smoking on ankle brachial index
Authors: Zahra Hessami, Babak Sharif Kashani, Hooman Sharifi, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2013)

Introduction:   Recently hookah smoking has increased in Iran and this trend continues to be a serious problem for the population health especially among adolescents. There is a wrong attitude that hookah smoking is safer than cigarette smoking.   Aims and objective:   We aimed to evaluate acute effect of hookah smoking on ankle brachial index. This index is a non invasive measure of peripheral artery disease.  Methods:  The study design was a descriptive cross sectional, before –after, to assess the acute effect of hookah smoking among participants. The participants included healthy volunteer subjects who didn’t have any underlying medical disease. They had experience of hookah smoking.  Ankle brachial index was measured before and after of hookah smoking by using an automatic device. Data were analyzed using SPSS software.  Results:  Twenty nine persons participated in this study. All of them experienced hookah. The mean age of them was 32.2±9.09. The mean of ankle brachial index before hookah smoking was 1.06±0.1 whereas it was 0.88±0.1 after hookah consumption. P=0.001   Conclusion:   Hookah smoking had acute effect on ankle brachial index. This index reduced after hookah consumption significantly. Therefore this type of tobacco product could be associated with the possibility of coronary artery disease. It suggests more study in this regard.
Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease
Authors: Stephen J. Murphy, Steven N. Hart, Geoffrey C. Halling, Sarah H. Johnson, James B. Smadbeck, Travis Drucker, Joema Felipe Lima, Fariborz Rakhshan Rohakhtar, Faye R. Harris, Farhad Kosari, Subbaya Subramanian, Gloria M. Petersen, Timothy D. Wiltshire, Benjamin R. Kipp, Mark J. Truty, Robert R. McWilliams, Fergus J. Couch, George Vasmatzis
Journal: Cancer Research (2015)

Abstract Many somatic mutations have been detected in pancreatic ductal adenocarcinoma (PDAC), leading to the identification of some key drivers of disease progression, but the involvement of large genomic rearrangements has often been overlooked. In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Integration of data from MPseq, exome sequencing, and transcriptome analysis of primary PDAC cases identified limited overlap in genes affected by both rearrangements and point mutations. However, significant overlap was observed in major PDAC-associated signaling pathways, with all PDAC exhibiting reduced SMAD4 expression, reduced SMAD-dependent TGFβ signaling, and increased WNT and Hedgehog signaling. The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression. Cancer Res; 76(3); 749–61. ©2015 AACR.
Abstract 11126: Elimination of Sources for Human Atrial Fibrillation (Focal Impulse and Rotor Modulation, FIRM) Organizes and Acutely Terminates AF Prior to Pulmonary Vein Isolation: A Multicenter Experience
Authors: Sanjiv M Narayan, John D Day, Kenneth Ellenbogen, John Hummel, Robert C Kowal, David E Krummen, John M Miller, Vivek Y Reddy, Kalyanam Shivkumar, Jonathan S Steinberg, Kevin R Wheelan
Journal: Circulation (2012)

Introduction: This 9-center study tested the hypothesis that panoramic (wide-area) electrophysiological mapping of both atria would reveal localized rotors and focal sources that sustain human AF, ...