tbuckley/cabot-search huggingface dataset:
Tamoxifen-related endocrine symptoms in early breast cancer patients are relieved when it is switched to anastrozole
Authors: C. Massacesi, L. Zepponi, M. B. Rocchi, S. Rossini, L. Burattini
Journal: Journal of Clinical Oncology (2006)

10597 Background: To determine how menopausal symptoms and quality of life changed when adjuvant tamoxifen has been suspended for any reason in favor of anastrozole in early breast cancer (BC) patients (pts). Methods: Major inclusion criteria: severe side effects or serious potential diseases caused by tamoxifen (20 mg die) that switched to anastrozole (1 mg die); confirmed early BC radically resected and with positive hormonal receptors; postmenopausal status; adjuvant chemo and/or radiotherapy suspended at least 4 wks before the hormonal switch. Exclusion criteria: discontinuation of tamoxifen for endocrine symptoms. Menopausal symptoms and health-related quality of life were assessed by the series of Functional Assessment of Cancer Therapy-Breast (FACT-B) plus endocrine subscale (ES) questionnaires at the switch and 3, 6, 9, and 12 months later. Sample size was decided by the effect size method (SD fixed as 0.5, effect of medium value). Score modifications were evaluated by one-way ANOVAS. Results: From Feb 2002 to Jun 2003, a total of 44 women were enrolled into the study. Discontinuation of tamoxifen was for: asymptomatic uterine problems (endometrium thickening or fibromatosis) in 56% of pts; cardiovascular disorders (mainly leg thrombosis and phlebitis) in 18%; patient’s refusal in 9%; GI persistent side effects in 5%; other reasons in 12% of pts. Endocrine symptoms ameliorated between baseline and 3 months, and stabilized thereafter. Mean ES scores improvement from baseline test was +3 (95% CI, 1 to 5), +4 (95% CI, 3 to 6), +5 (95% CI, 3 to 7), and +4 (95% CI, 3 to 6) at 3, 6, 9 and 12 months, respectively. FACT-ES global score had a mean improvement during 1-yr period of 9 points (95% CI 6 to 13, p &lt; .0005), with 22 patients (50%) ever reaching an increase ≥ 5% of the baseline score. There also was a significant improvement in TOI score (+4 points, 95% CI 2 to 6, p &lt; .0005), and physical and breast cancer subscales (+2, 95% CI 1 to 2, p &lt; .001, and +1, 95% CI, 1 to 2, p &lt; .001, respectively). Pts receiving anastrozole reported higher rate of mild arthritic and bone pain (27% vs 7%, p = .021). Conclusion: When a patient develops an endocrine symptom while on tamoxifen, a change in favor of anastrozole should be considered to minimize those symptoms and to improve quality of patient’s life. No significant financial relationships to disclose.
The circadian profile of melatonin secretion in patients with OSAS
Authors: Malgorzata Barnas, Ryszarda Chazan
Journal: European Respiratory Journal (2011)

Introduction: There is evidence to suggest that certain endocrine disorders are associated with impaired breathing during the sleep. One of the hormones closely associated with sleep is melatonin. It is a hormone secreted cyclically, which controls the rhythm of sleep and waking.

Aim: Aim of the study was to investigate circadian profile of melatonin secretion in patients with OSAS.

Methods: Study group consisted of 71 patients with OSAS: 66 men (93%) and 5 women (7%). The average age was 49,2±9,1 years. Body mass index was 32,7±5,9 kg/m2,mean AHI 45±22,8/hour. OSAS was diagnosed with full polysomnography. In the study group 6 patients (8,45%) diagnosed with mild OSAS, 10 patients (26,76%) moderate OSAS and 46 patients (64,89%) severe OSAS. Control group consisted of 18 subjects with excluded OSAS, mean age 43±13 years, mean BMI 28,7±4 kg/m2, mean AHI 2,5±2,1. In the study group and control group circadian profile of melatonin secretion was assessed with radioimmunoassay method (RIA) at 6 time points.

Results: Melatonin concentration (pg/ml) at 2.00, 6.00, 10.00 am, and 2.00, 6.00, 10.00 pm were: in the study group 91,8±70,7, 63,2±54,8, 21,4±11,3, 17±8,3, 21,1±16,2, 50,1±40,6, and in the control group 136,7±93,9, 94,2±75,5, 30,4±29,5, 13,9±6,1, 16,5±11,9, 43,6±27,6 respectively. In the study group mean concentration of melatonin at 2.00 am and 6.00 am was significantly lower than in the control group, p=0,04 and p=0,02 respectively.

Conclusion: Patients with OSAS have preserved circadian rhythm of melatonin secretion, with peak secretion at night hours. The maximum concentration of melatonin at night is significantly lower than in the healthy group.
Viability of the Human Cervical Epithelium With Dysplasia and Carcinoma In Situ 2
Authors: C. A. Rubio, B. Lagerlöf, Y. Kock, G. Söderberg, P. Thomassen
Journal: JNCI Journal of the National Cancer Institute (1978)

Autoradiograms of histologic slides of 58 human cone specimens with dysplasia and carcinoma in situ were analyzed after tissue samples were incubated with labeled RNA precursors. Both the vertical and lateral distributions of labeled cells were rather uniform in the major part of the epithelium, which suggested that the tissue remained metabolically active during incubation. Only the uppermost epithelial cells in heavily labeled areas were devitalized as deduced by the morphologic appearance of the cells, the absence of labeling in the cells, the trypan blue exclusion test, and the trypsin digestion test. The viability of large epithelial areas suggested that the previously reported focal distribution of proliferating and nonproliferating areas in the cervical epithelium is a genuine phenomenon and not the result of focal epithelial devitalization acquired during incubation.
Stage I nonfunctioning neuroendocrine tumors of the pancreas: Surgery or surveillance?
Authors: J. R. Strosberg, A. Cheema, L. K. Kvols
Journal: Journal of Clinical Oncology (2011)

349 Background: An increasing number of nonfunctioning, early-stage pancreatic neuroendocrine tumors are detected incidentally as patients undergo radiographic procedures for unrelated indications. Endoscopic sonography with fine-needle aspiration now enables nonoperative biopsy of tumors smaller than 1 cm in diameter. It is unclear whether the risks of partial pancreatectomy or enucleation exceed the risks of surveillance in patients with these neoplasms. Methods: We performed a database search of patients with pancreatic neuroendocrine tumors treated at the H. Lee Moffitt Cancer Center in order to evaluate outcomes of patients with stage I tumors who did not undergo surgical resection. Results: Four patients were identified who elected to undergo surveillance of their stage I tumors instead of surgical resection. All had been diagnosed via endoscopic ultrasound-guided fine-needle aspiration. The tumor sizes were 7 mm, 12 mm, 13 mm, and 15 mm at initial diagnosis. Three tumors were cystic and one was solid. Three were located in the body of the pancreas and one in the tail. In two patients, the Ki-67 index was measured and was &lt;1%. With a median of follow-up of two years, none of the patients experienced tumor growth. All three patients with cystic tumors experienced shrinkage of their tumors following the diagnostic needle aspiration and did not experience subsequent increase in size (Table). Conclusions: Surveillance may be an appropriate strategy for management of incidentally discovered, stage I pancreatic neuroendocrine tumors. [Table: see text] No significant financial relationships to disclose.
Natural Killer Cell Activity and Head and Neck Cancer: A Clinical Assessment&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S P Schantz, E J Shillitoe, B Brown, B Campbell
Journal: JNCI Journal of the National Cancer Institute (1986)

In 127 patients with squamous cell carcinoma of the upper aerodigestive system, an assessment of natural killer (NK) cell function was performed. The mean lytic unit (LU) value of this cancer population was noted to be less than the mean value of 67 age-matched controls assessed concurrently. The major determinant of cytolytic function was related to the growth pattern of the tumor. Increased NK cell function was observed in patients with lesions that were more locally or regionally aggressive, i.e., that infiltrated surrounding anatomic structures. The magnitude of NK cell response also correlated with increased amounts of circulating IgG immunoglobulin to herpes simplex virus-type 1-associated antigens; elevated IgG levels were also associated with locally aggressive lesions. The clinical significance of NK cell activity in these patients is shown by its relationship to disease-free prognosis. Patients with elevated NK activity followed for a mean of 12 months had an improved disease-free survival as compared to the survival of the remaining population. Furthermore, NK LU values were not reflected in standard staging methods, which suggests that the measurement of NK cell function represents an independent prognostic parameter in the patient with head and neck cancer.
International Union of Pharmacology nomenclature of endothelin receptors.
Authors: T Masaki, J R Vane, P M Vanhoutte
Journal: Pharmacological Reviews (1994)

Following the discovery of ET (Yanagisawa et a!., 1988), the existence of three distinct isoforms of ET, designated ET-1, ET-2, and ET-3, was predicted from the finding of three separate genes (Inoue et al., 1989). The expression of the three isotypes has been verified in many tissues and found to occur in various proportions. Only ET-1 is made by endothelia! cells. In addition to these endogenous ligands, sarafotoxins, constituents of a rare snake venom, have been included as members of the ET superfamily. ETs act not only on blood vessels but also in nonvascular systems. These diverse responses to ETs appear to be mediated by specific receptors. Results of many pharmacological and ligand-binding expemiments have suggested the existence of multiple subtypes
Impact of S-1 plus cisplatin neoadjuvant chemotherapy in scirrhous gastric cancer.
Authors: Chikara Kunisaki, Hirochika Makino, Jun Kimura, Ryo Takagawa, Amane Kanazawa, Takashi Oshima, Mitsuyoshi Ota, Takashi Kosaka, Hidetaka Ono, Hirotoshi Akiyama, Itaru Endo
Journal: Journal of Clinical Oncology (2015)

198 Background: This study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3 week regime of the fluoropyrimidine, S-1 (40 mg/m 2 , orally, twice daily), with cisplatin (60 mg/m 2 , intravenously, day 8) were administered to patients, separated by a 2 week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n=27). We compared overall survival and prognostic factors in these patients with a non-neoadjuvant group (n=19). Results: For all patients, univariate analysis identified non-curative gastrectomy and positive lavage cytology as adverse prognostic factors; extended lymph node dissection was a positive prognostic factor. Multivariate analysis showed that non-curative resections independently influenced prognosis (hazard ratio=2.902, p=0.011). In the SP group, positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after SP chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusions: After SP neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.
Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome
Authors: Alan C. Braverman, Kevin M. Harris, Richard J. Kovacs, Barry J. Maron
Journal: Circulation (2015)

A cute aortic dissection or rupture in Marfan syndrome or other aortopathies is an important cause of sudden death in athletes. 1Increased blood pressure and aortic stress during intense physical exertion place the patient with Marfan syndrome, Loeys-Dietz syndrome, familial thoracic aortic aneurysm (TAA) and dissection syndrome, bicuspid aortic valve (BAV) aortopathy, aortic aneurysm, or other genetically triggered aortic diseases at risk for aortic catastrophe from aortic dissection or rupture or may accelerate aneurysm formation.Therefore, for people with aortic disease or a condition associated with aortic disease, discussion about safe levels of low-intensity, noncompetitive exercise should be emphasized beginning at a young age.This is important for a healthy lifestyle and to prevent social stigmatization, which may occur when physical activity is restricted excessively in young people.Marfan syndrome, an autosomal dominant disorder of connective tissue with an estimated prevalence of 1 in 5000 to 10 000, is caused by abnormal fibrillin-1 attributable to mutations in the FBN1 gene. 2 Manifestations involve multiple organ systems, including the aorta, heart and valves, skeleton, eye, lungs, and dura.FBN1 mutations can be identified in the vast majority of patients satisfying the revised Ghent criteria for Marfan syndrome. 2The diagnosis of Marfan syndrome is made by use of clinical criteria, imaging, family history, and genetic testing as outlined in the revised Ghent criteria (Tables 1 and2). 2Cardiovascular features of Marfan syndrome include mitral valve prolapse, mitral regurgitation, aortic root dilatation (most pronounced at the sinuses of Valsalva), and aortic dissection. 2 The descending aorta, although less commonly involved in young patients, is also at risk for aneurysm formation and dissection.Other genetically triggered aortic aneurysm syndromes and conditions associated with aortopathy may increase the risk of aortic dissection in competitive athletes.Loeys-Dietz syndrome is caused by mutations in TGFBR1 and TGFBR2 and is characterized by craniofacial features, arterial tortuosity, and aneurysms
Epidermal Growth Factor Receptor (Egfr) and Abcg2 Polymorphisms and Treatment Outcome in the Randomized Phase III Torch Trial in Advanced Non-Small Cell Lung Cancer (Nsclc) Patients
Authors: G. Liu, M. Di Maio, M. Tsao, D. Cheng, Z. Chen, R. Wierzbicki, F. Riccardi, M. Spatafora, V. Adamo, A. Favaretto, R. Bianco, R.W. Gregg, R. Costanzo, S. Signoriello, C.A. Butts, F. Ciardiello, R. Feld, C. Gallo, C. Gridelli, F. Perrone
Journal: Annals of Oncology (2014)
Invasive healthcare-associated (HA) environmental fungal infections (EFI) in pediatric oncology (ONC) patients (PTS) are an ever-present risk
Authors: J. Cox, P. Metcalf, J. Seigel, N. Winick
Journal: Journal of Clinical Oncology (2007)

19631 To reduce the risk of HA EFI, our ICUs, onc inpatient and stem cell transplant (SCT) units are centrally HEPA filtered and portable HEPA filters are used in each onc outpatient clinic room. Anticipating demolition and then construction of a new, adjacent hospital tower, infection control (IC) verified (Feb 2006) that all windows were completely sealed, provided valet parking remote to the construction and N95 respirators to be worn in all areas except the HEPA filtered locations for immunosuppressed pts to reduce exposure to construction dust; a known risk factor for HA EFI. Eleven new cases of possible HA EFI were diagnosed in 2006: 3 part of a Jan-Feb cluster related to a new construction elevator and malfunction of a door to the outside and 8 clustered July-Oct after demolition and construction began in April. This compares with only 4 cases in 2005. The primary diagnoses in 2006 were AML (6), ALL (4), and hemophagocytic lymphohistiocytosis (1) versus AML (2) and SCT (2) in 2005. Pts with AML and SCT received antifungal prophylaxis or were receiving antifungal therapy at the time of EFI diagnosis. Different isolates were identified including Aspergillus (numerous species), Scedosporium, Fusarium, and Rhizopus; sites of infection included paranasal sinuses (5), pulmonary (6), skin (2) and GI tract (1). 3 of 11 pts died; all required long term antifungal therapy, and most required altered chemotherapy. 4 of 8 pts in the Jul-Oct cluster had been in rooms later found to have faulty window caulking caused by severe weather conditions in Mar 2006. Our data suggest that despite implementation of measures to prevent HA EFI, new sources of outside air and construction dust likely led to an increase in HA EFI. The absence of HA EFI in SCT pts in 2006 may be attributed to the positive pressurization of the SCT unit, location of the unit facing away from the construction site and the antifungal prophylaxis used. The variety of fungi also support outside air as a source. After the faulty caulking was identified and repaired, no further HA EFI occurred; a case-control study is underway to identify important risk factors. Vigilance for potential new sources of contaminated air is required on units with high risk patients. No significant financial relationships to disclose.
Identification of potential cancer targets from diagnostic and prognostic gene signatures
Authors: G. Vansant, K. Oades, M. Pickering, J. Monforte
Journal: Journal of Clinical Oncology (2006)

20096 Background: The purpose of this study was to determine the potential of gene signature development to also identify leads among different tumor types compared to normal cells. The theory is that cancer cells will express unique markers that are related to their growth and metastatic potential and therefore be potential targets for therapeutics. Methods: Multiplex PCR Approximately 100 genes were chosen to produce 3 multiplexes for RT-PCR analysis. These genes were identified from gene signatures found in peer reviewed manuscripts. RT and PCR primer pairs designed for each gene to be monitored are chimeric, with a gene specific sequence and a universal sequence common to all forward and reverse primers, respectively. A pair of universal primers that recognize the universal sequences in the chimeric primers are included in the reaction in great excess, with one fluorescently labeled. After reverse transcription and a few rounds of PCR, these universal primers drive the reactions, so all the PCR products are essentially amplified by the universal primer set. The chimeric primers are designed to produce PCR products that all have a difference in length of approximately 5 base pairs, resulting in a stratified set of labeled PCR products. 25ng of total RNA from each tumor derived cell line was used as template for the reverse transcription reactions. Half of these reactions were carried over as templates for the PCR reactions. The PCR products were fluorescently labeled during the PCR reaction and analyzed on a capillary electrophoresis system. Results: Many genes were expressed at high levels across all cancer cell types compared to control cells including an A kinase anchoring protein, cyclin-E2, JPO1, mucin 1, and the transferrin receptor CD 71. Conclusions: Analysis of the expression of genes that are part of diagnostic and prognostic gene signatures in tumor related cell lines revealed many genes whose expression were altered in tumor derived cells that are potentially related to the ability of the carcinogenic cells to proliferate and metastasize. Subsequently, a secondary benefit of the development of prognostic or diagnostic gene signatures with statistical analysis, may be the elucidation of potential therapeutic targets for the treatment of cancer. No significant financial relationships to disclose.
Effects of celecoxib on vascular endothelial growth factor (VEGF) gene expression in squamous cell carcinoma of head and neck (SCCHN) patients receiving 5-fluorouracil and cisplatin
Authors: C.-T. Hsueh, C.-F. Chiu, S.-P. Yeh, Y.-M. Liao
Journal: Journal of Clinical Oncology (2005)

5603 Background: Induction of cyclooxygenase-2 (COX-2) gene expression in SCCHN cells results in an increase in VEGF expression. Several phase II studies using celecoxib, a selective COX-2 inhibitor, in combination with chemotherapy have shown to increase chemotherapy efficacy in patients with non-small cell lung and colorectal cancers. The purpose of this pilot study is to examine VEGF gene expression in SCCHN patients receiving celecoxib and chemotherapy with an intention to develop a novel therapeutic regimen. Methods: This is an open-label one-arm phase II study with ongoing accrual. Recurrent or metastatic SCCHN patients who meet the eligibility criteria are given celecoxib 400mg po bid starting 3 days before first course of chemotherapy and continuing through out study period. Chemotherapy is repeated every 28 days with cisplatin 100 mg/m2 IV infusion 2 hours on day 1, then 5-fluorouracil 1000 mg/m2 IV infusion 24 hours daily for 5 days. Evaluation of treatment response is conducted after 3 cycles of chemotherapy. Twenty ml blood sample and 24-hour urine are collected on 4 days prior to 1st cycle of chemotherapy (before taking celecoxib), day 1 and day 5 of each chemotherapy cycle, and are subject to VEGF and PGE2 measurement by enzyme immunoassay kits from Amersham. Additionally, peripheral blood mononuclear cells are used for VEGF RT-PCR. Results: We have analyzed the first 3 patients’ blood samples for VEGF gene expression. One patient’s VEGF gene expression remained unchanged during the first and second cycles of treatment. Two patients’ VEGF gene expression increased 1.5- to 2-fold by the end of first cycle, and increased to four-fold by the end of 2nd cycle. All three patients were found to have progression of disease. Analysis of serum prostaglandin E2 is ongoing. Further results will be presented. Conclusions: Celecoxib can not effectively suppress induction of VEGF gene expression in SCCHN patients receiving chemotherapy with cisplatin and 5-fluorouracil, and may not enhance chemotherapy efficacy in this setting. Future study using celecoxib and VEGF inhibitor in combination with chemotherapy in SCCHN is planned. No significant financial relationships to disclose.
A phase I-II study of bialkylator chemotherapy, high-dose thiotepa, and cyclophosphamide with autologous bone marrow reinfusion in patients with advanced cancer.
Authors: S F Williams, J D Bitran, L Kaminer, C Westbrook, R Jacobs, J Ashenhurst, E Robin, S Purl, J Beschorner, C Schroeder
Journal: Journal of Clinical Oncology (1987)

Twenty patients with disseminated cancer both untreated and previously treated received bialkylator chemotherapy, thiotepa, and cyclophosphamide and reinfusion of cryopreserved autologous bone marrow (ABMR). The cyclophosphamide dose was constant at 7.5 g/m2 over three days, while thiotepa was started at 1.8 mg/kg for three days in escalating dose by a modified Fibonacci schema to 7 mg/kg. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets/microL was 18 and 27 days, respectively. Four patients died as a consequence of severe, overwhelming infections or progressive disease during their period of aplasia. Of the 18 evaluable patients, a complete response (CR) was achieved in three patients and a partial response (PR) in ten patients for an overall response rate of 72%. The median duration of response was 14 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, stomatitis, skin rash, and cardiomyopathy. The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses. Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer.