tbuckley/cabot-search huggingface dataset:
Polymorphisms in DNA repair genes and familial colorectal cancer risk
Authors: I. Blanco, S. Gonzalez, E. Guinó, G. Capellá, V. Moreno
Journal: Journal of Clinical Oncology (2008)

22226 Background: Hereditary colorectal cancer (CRC) has been related to mutations in APC, mismatch repair genes and base excision repair genes, but little is known about the risk of developing CRC associated to common polymorphisms in these genes. We conducted a case control study to assess the risk of common polymorphisms in DNA repair genes in relation to hereditary CRC. Methods: A total of 278 cases with pathology-verified CRC were ascertained through a cancer family clinic: 35 HNPCC, 186 HNPCC-Like and 57 had other familial aggregation patterns (FACCR). The control population group (n=329) was a hospital-based reference population for a case-control study of sporadic CRC (Moreno V et al. Clin Cancer Res 2006; 12: 2101–8). Eleven common polymorphisms were studied: MLH1 (I219V, ic.453+79A>G; c.1668–19A>G), MSH2 (c.211+9C>G, c.2006–6T>C), OGG1 (S326C), MYH (G382D and Y165C), XRCC1 (Q399R and R194W) and ERCC2 (L751Q). Genotype frequencies were compared with logistic regression models using several inheritance models and haplotypes were estimated with the EM algorithm. Results: None of the polymorphisms was individually significantly associated with CRC. However, all 3 polymorphisms in MLH1 were in high linkage disequilibrium and showed an elevated risk, especially ic.453+79A>G in intron 5 (odds ratio per allele= 1.25; 95% CI: 0.99–1.58, P=0.056). The 3 variant alleles shared a common haplotype (G-G-G) with estimated frequency of 35% and an odds ratio of 1.31 (95% CI 1.02–1.69; P=0.037) in an additive model. Polymorphisms OGG1 S326C and MYH Y165C also showed increased risks that did not reach statistical significance. The analysis restricted to HNPCC cases showed greater associations with MHL1 (ic.453+79A>G and c.1668–19A>G) alleles [OR per allele of 2.05 (95% CI: 1.23–3.44; P=0.0047] and MSH2 alleles (c.2006–6T>C) OR=2.53 (95% CI: 1.32–4.88; P=0.0078). Similar high ORs were observed for cases carriers of germline mutations in mismatch repair genes. Conclusions: Although the overall impact of common polymorphisms in DNA repair genes in familial colorectal cancer etiology seems limited, MHL1, MSH2, OGG1 and MYH may harbor cancer susceptibility polymorphisms. No significant financial relationships to disclose.
Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), in previously treated patients with malignant pleural mesothelioma (MPM)
Authors: V. Gregorc, G. L. Ceresoli, P. A. Zucali, F. G. De Braud, E. Bajetta, A. Santoro, M. G. Viganò, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2009)

7582 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N (CD13) overexpressed on tumor blood vessels. In preclinical models, NGR-hTNF has shown potent anti-vascular and antitumor activity, both at low and at high doses. Methods: Patients with advanced MPM were treated with a low-dose of NGR-hTNF given intravenously at 0.8 μg/m 2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and a total of 27 patients to be enrolled after first and second stage, respectively. Primary endpoint was progression-free survival (PFS) with restaging performed q6w according to MPM-modified RECIST criteria. Results: From May 2007 to January 2008, forty-three patients with radiologically-documented progressive disease after a pemetrexed-based regimen were evaluated over 167 cycles (range, 1 to 17). Patient characteristics were: median age 64 years (range, 54 to 80); male/female 27/16; epithelial/non-epithelial histology 34/9; PS 0/1/2 24/10/9; EORTC score good/poor 34/9. Main grade 1–2 toxicity was chills (71%), transiently occurring after the first infusions. Only one grade 3 treatment-related toxicity was observed. One patient (2%) had a partial response lasting 7.1+ months and 17 patients (40%) maintained stable disease for a median duration of 4.4 months (range, 1.3 to 12.4+ months). The median and 3-month PFS were 2.8 months and 43%, respectively, whereas the median and 1-year overall survival were 11.6 months and 48%, respectively. In an additional 14 patients treated at same dose with a weekly schedule, there was any suggestion of toxicity exacerbation. In this cohort, the PFS rate at 6 months was 36%, with 7 patients (50%) experiencing stable disease for a median duration of 6.9 months (range, 2.4 to 9.3+ months). Conclusions: NGR-hTNF 0.8 μg/m 2 weekly is well tolerated, showing prolonged disease control in previously treated MPM patients, and will be further developed in this setting. [Table: see text]
Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.
Authors: W Aulitzky, G Gastl, W E Aulitzky, M Herold, J Kemmler, B Mull, J Frick, C Huber
Journal: Journal of Clinical Oncology (1989)

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.
Abstract 16683: Reduced Lung Function is Associated With Decreased Ejection Fraction and Decreased Left Ventricular Size in Patients in a Tertiary Care Center
Authors: Melissa S Burroughs Pena, Michael Durheim, Phillip Schulte, Peter Kussin, William Checkley, Eric J Velazquez
Journal: Circulation (2014)

Background: Pulmonary disease has been associated with poor cardiovascular outcomes including heart failure; yet, the relationship between measures of obstructive and restrictive lung disease as defined on pulmonary function testing (PFT) and left ventricular size and function remains unknown. The objective of this study is to determine the correlation between forced expiratory volume/1 sec (FEV1), forced vital capacity (FVC) and FEV1/FVC with left ventricular ejection fraction (LVEF), internal diastolic diameter (LVIDD), and internal systolic dimension (LVISD) as measured by transthoracic echocardiography (TTE). Methods: We selected patients who underwent both TTE and PFT within 7 days from January 2012 to April 2013. We examined for bivariate relationships by using Pearson’s correlation coefficient to determine associations between pre-bronchodilator FEV1, FVC and FEV1/FVC and the following TTE measures: LVEF,LVIDD, and LVISD. Multivariable regression analysis was used to adjust for age and sex. Results: We identified 2238 patients who had TTE and PFT within 7 days. After adjusting for age and sex, FEV1, FVC, and FEV1/FVC were positively correlated with LVEF and LVIDD. Every 100 cc reduction in FVC or 90 cc reduction in FEV1 was associated with a 5% decrease in LVEF (95% CI 0.079- 0.128, 0.068- 0.109). Moreover, a 200 cc reduction in FEV1 or 220 cc reduction in FVC was associated with a 1 cm decrease in LVIDD (95% CI 0.152- 0.247, 0.165- 0.282,). These correlations remained significant when percent predicted instead of absolute FEV1 and FVC were evaluated. Conclusion: Abnormal lung function is associated with reduced LV function without corresponding increases in ventricular size. These findings suggest that the association between pulmonary disease and heart failure may not depend on adverse ventricular remodeling and requires further study.
Enhancement of therapeutic effect in combination treatment with imatinib and anticancer drug in gastric carcinoma
Authors: R. Kim, M. Emi, K. Tanabe, T. Toge
Journal: Journal of Clinical Oncology (2004)

4163 Background: Imatinib (STI571, Gleevec) is a novel molecular targeting agent, which inhibits the activity of c-kit and PDGFR in gastrointestinal stromal tumors. We conducted preclinical evaluation of therapeutic effect of imatinib and potential synergism in combination with imatinib and anticancer drug in gastric carcinoma cells, in terms of growth inhibition by targeting PDGF/PDGFR signaling pathway. Materials and Methods: MKN-45 gastric carcinoma cells were employed, and the cells were transplanted into nude mice. When the tumor size was reached approximately 100 mm3 after transplantation, the mice were arbitrarily divided in four groups (n=8/group), according to no treatment, treatment with anticancer drug alone, treatment with imatinib alone, and combination treatment with imatinib and anticancer drug, respectively. Imatinib was administered intraperitoneally at 50 mg/kg for consecutive 28 days, whereas anticancer drug was administered at LD50/3 four times in qwk. Results: The treatment with imatinib of MKN-45 gastric carcinoma xenograft showed antitumor effect to a greater extent than the treatment with 5-fluorouracil (5-FU) or docetaxel (TXT) alone. Further, antitumor effect was significantly enhanced in the combination treatment with imatinib and 5-FU or TXT, compared to the treatment with imatinib, 5-FU or TXT alone (P<0.01, Student t-test). Enhanced antitumor effect in combination treatment with imatinib and anticancer drug was associated with both induction of apoptosis and inhibition of tumor angiogenesis, which was explained with the decreased expression in pAkt, and PDGF-betaR, and decreased phosphorylation of PDGF-betaR. Conclusions: Combination treatment with imatinib and anticancer drugs such as 5-FU and TXT may a new strategy for enhancing therapeutic effect in the treatment of gastric carcinoma, targeting inhibition of PDGFR-mediated paracrine tumor growth. No significant financial relationships to disclose.
Induction of DNA Repair Synthesis in Human Urothelial Cells by the &lt;italic&gt;N&lt;/italic&gt;-Hydroxy Metabolites of Carcinogenic Arylamines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: C Y Wang, B Christensen, K Zukowski, K C Morton, M S Lee
Journal: JNCI Journal of the National Cancer Institute (1984)

Urinary N-hydroxy metabolites of carcinogenic arylamines were investigated for their abilities to induce unscheduled DNA synthesis (UDS) in human urothelial cell lines HCV 29, HU 1734, and HU 1752, and in a primary culture of human urothelial cells. N-Hydroxy-2-aminofluorene (CAS: 53-94-1; N-OH-AF), N-hydroxy-2-acetylaminofluorene (CAS: 53-95-2; N-OH-AAF), and the N-glucuronide of N-OH-AF induced UDS in HCV 29, HU 1734, and HU 1752. N-Hydroxy-4-aminobiphenyl (CAS: 6810-26-0; N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (CAS: 4463-22-3; N-OH-AABP), N-hydroxy-2-aminonaphthalene (CAS: 613-47-8; N-OH-AN), N-hydroxy-2-acetylaminonaphthalene (CAS: 2508-23-8; N-OH-AAN), and the N-glucuronide of N-OH-ABP induced UDS in HCV 29. However, the N-glucuronide of N-OH-AN did not. The O-glucuronide of N-OH-AAF induced UDS in HCV 29 only when beta-glucuronidase was present. Paraoxon inhibited the induction of UDS in HCV 29 by N-OH-AAF and N-acetoxy-2-acetylaminofluorene (CAS: 6098-44-8), but not by N-OH-AF. When examined in a primary culture of human urothelial cells, N-OH-AF, N-OH-AAF, N-OH-ABP, and N-OH-AABP were active, but N-OH-AN, N-OH-AAN, 2-aminonaphthalene (CAS: 91-59-8), 2-aminofluorene (CAS: 153-78-6;), and 4-aminobiphenyl (CAS: 92-67-1) were not. These results demonstrate that human urothelial cells are able to activate both acetylated and non-acetylated N-hydroxy metabolites of carcinogenic arylamines, and they suggest that O-glucuronidation may be a detoxification mechanism for N-arylacethydroxamic acids.
Kwashiorkor--II. Clinical Picture, Pathology, and Diagnosis
Authors: H. C. Trowell, J. N. P. Davies, R. F. A. Dean
Journal: BMJ (1952)

Kwashiorkor appears to be one of the major nutri- tional diseases.It has been recognized by many African tribes, who have their own names for it.In many parts of the Tropics and sub-Tropics the disease is extremely common.It attacks children at a time when their protein requirements are high.The disease has been described not only in Africa but also in tropical America and in Asia, and may occur in some of the poorer towns of southern Europe.Although African children grow well while fully breast-fed, many of them fail to put on weight satisfactorily, develop brown hair, and have attacks of diar- rhoea in the weaning and post-weaning periods.These children are believed to suffer from mild kwashiorkor.Tropical infections complicate but do not cause kwashiorkor.
Gamma Knife stereotactic radiosurgery in the treatment of brain metastases from breast cancer
Authors: R. Gutt, S. Yovino, L. Chin, W. Regine, P. Amin, K. Tkaczuk, Y. Kwok
Journal: Journal of Clinical Oncology (2006)

10555 Background: Outcomes of gamma knife stereotactic radiosurgery (GK-SRS) for patients with brain metastases specifically from breast cancer have not been well-defined. This study was undertaken to report the long-term experience with GK-SRS in this subset of patients. Methods: From 1995 to 2005, 75 patients with 162 brain lesions were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up data were available in 65 patients. Additional whole brain radiation therapy (WBRT) was administered to 53 (81.5%) patients. The median WBRT dose was 36.75 Gy (30.0–45.0 Gy). The median number of lesions treated with GK-SRS was 2 (1–8 lesions). The median follow-up, age, and KPS were 7.2 months (0.4–75.7 months), 53.5 years (23–81 years), and 90 (40–100), respectively. The factors included in the univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) were age, Karnofsky Performance Status (KPS), tumor histology, estrogen receptor status, Her-2-neu status, number of intracranial lesions, and presence of systemic disease. Results: Median PFS and OS from GK-SRS were 5.3 months (0.4–33.2 months) and 8.1 months (0.4–75.7 months), respectively. The 6, 12, and 24 month actuarial PFS were 47.8%, 24.9%, and 9.6% respectively. The 6, 12, and 24 month actuarial OS were 60.7%, 39.1%, and 18.1% respectively. The tumor local control after WBRT and GK-SRS was 87.7%. Radiation necrosis was a complication in 10.8% of patients. Forty-seven (72.3%) patients had neurological symptoms prior to gamma knife treatment. Seven (14.9%) and 9 (19.1%) of these patients experienced symptom resolution and significant symptomatic improvement, respectively. Multivariate and univariate analysis did not reveal any of the prognostic factors in question to be significantly associated with OS nor PFS. Conclusions: This relatively large cohort of patients experienced poor survival outcomes despite aggressive therapy with WBRT and GK-SRS. However, GK-SRS can provide significant symptomatic relief, with acceptable complication rates. More research is required to improve the survival of breast cancer patients with intracranial metastases. No significant financial relationships to disclose.
Validity of the modified RECIST criteria and EORTC PET criteria evaluated based on the pathologic findings for patients with resectable malignant pleural mesothelioma
Authors: T. Mimura, H. Watanabe, T. Yamanaka, M. Satouchi, M. Okada
Journal: Journal of Clinical Oncology (2009)

e11639 Background: The unique growth pattern of malignant pleural mesothelioma (MPM) presents challenges for clinical investigators evaluating the responses to chemotherapy, which is an important surrogate endpoint for patient benefit, particularly in clinical trials. In patients with resectable MPM, multicenter clinical trials of neoadjuvant chemotherapy followed by extrapleral pneumonectomy (EPP) and subsequent radiotherapy have been attempted around the world. The applicability of modified RECIST based on the findings on CT images and EORTC (European Organization for Research and Treatment of Cancer) criteria based on the findings on FDG-PET images to resectable MPM would be challenging and significant, but their validity has never been examined. Methods: Between May 2006 and November 2008, 13 consecutive patients with resectable pathologically proven MPM were included in this study. All were initially treated with combination chemotherapy including cisplatin. EPP was successfully performed in all the patients. In addition to modified RECIST (CR vs PR vs SD vs PD), FDG uptake by the tumor on PET was also evaluated according to the EORTC PET criteria (CMR vs PMR vs SMD vs PMD). Also, pathologic findings (NT; no viable tumor vs MR; minimal residual vs GR; gross residual) were reviewed. Results: According to modified RECIST, in which the definition of measurable lesions is ≥10mm in diameter, 7 of the 13 patients investigated had no measurable lesion. Even when the definition of measurable lesions was changed to ≥5mm, 2 patients had no measurable lesion and 4 had only one lesion. In regard to the response, 4 of 11 patients with any measurable lesions were classified as PR, and 7 were classified as SD, while 8 patients were classified as PMR and 3 were classified as SMD according to the PET findings. Eight patients were classified as GR and 5 as MR. Kappa statistics suggested potential variation between the CT response and the pathologic findings (κ=0.214, 95% CI=-0.377 ∼ 0.806) and between the PET response and the pathologic findings (κ=0.286, 95% CI=-0.049 ∼ 0.620). Conclusions: Our data raise doubts about the validity of applying the modified RECIST criteria as well as EORTC PET criteria to resectable MPM. No significant financial relationships to disclose.
Cyclic Adenosine 3′ ,5′-Monophosphate-Binding Protein: Role in Ovariectomy-Induced Regression of a Hormone-Dependent Mammary Tumor in Sprague-Dawley Female Rats: Brief Communication 2
Authors: Yoon Sang Cho-Chung, Jeffrey S. Bodwin, Timothy Clair
Journal: JNCI Journal of the National Cancer Institute (1978)

Cyclic AMP- and estrogen-binding activities were present in 7,12-dimethylbenz[a]anthracene-induced mammary carcinomas in Sprague-Dawley female rats. Soon after ovariectomy of the host, cyclic AMP binding markedly increased and estrogen binding decreased in regressing tumors. These changes were reversed when tumor growth was resumed following the injection of estradiol-17beta. The data suggested the possible involvement of cyclic AMP binding in the growth control of a hormone-dependent mammary tumor.
Better training is needed on fetal alcohol disorders, says BMA
Authors: Susan Mayor
Journal: BMJ (2016)

Training programmes on the prevention, diagnosis, and management of fetal alcohol syndromes should be implemented for UK healthcare professionals and included in undergraduate curriculums to resolve a “scandalous lack of support” for the children affected, a report by the BMA has said.1

Developed by the BMA’s Board of Science, the report set out recommendations for the government, policy makers, and professionals to help prevent prenatal alcohol exposure and improve the lives of children born with fetal alcohol spectrum disorders.

The board’s chair, Sheila Hollins, said, “It has long been known that maternal alcohol …
Mitotic Rhythms in Human Cancer, Reevaluated by Electronic Computer Programs—Evidence for Chronopathology2
Authors: Mauricio Garcia-Sainz, Franz Halberg
Journal: JNCI Journal of the National Cancer Institute (1966)

Specially designed programs for the electronic computer providing useful displays of rhythms for research on cancer were applied to data published earlier by E. Tähti and A. Voutilainen. One such program, the cosinor, detected a statistically significant 24-hour-synchronized circadian rhythm in a set of serial mitotic counts on human mammary cancers but not in squamous or basal cell cancers before or after radiotherapy. Another program, the pooled variance spectrum, applied to the same series of mitotic counts obtained before radiotherapy, revealed that the variance was predominantly in the region of frequencies higher than one cycle in 20 hours, i.e., in the ultradian spectral region. By comparison, the contribution to the total variance from the circadian region, i.e., the contribution from frequencies lower than one cycle in 20 hours (equivalent to periods longer than 20 hours) was smaller. In those series obtained immediately following radiotherapy, analyzed by separate pooled variance spectra, the ultradian variance was reduced. The so-called “relatively-low-frequency quotient” was 30% for the data after radiotherapy and 20% for those before radiotherapy. The immediate response to radiotherapy of the spectrum of mitoses in certain human tumors, while confounded by possible effects of the serial biopsies, probably consisted of a selective reduction of the ultradian variance. The relative predominance of the ultradian variance over the circadian one in certain cancers of mature patients constitutes an aspect of the chronopathology of cancer, with a possible bearing on timing radiotherapy.
Preparations and Appliances
Authors: J COLLINGWOOD-STEWART
Journal: BMJ (1951)

REPORTS OF SOCIETIESMEDICAL OU151R 1 found in two patients that there had been a parallel rise in antibodies to both Coxsackie and poliomyelitis viruses during the course of the illness.The Coxsackie viruses were known to cause myositis in experimental animals, and it was possible that in man infection with this group of viruses might be related to the occurrence of muscular pain in the course of the illness.Symptomatology Dr. D. MCALPINE pointed out that in an epidemic only 1 to 2% of those infected with poliomyelitis virus became paralysed.Known factors determining the occurrence and the site of paralysis in an infected person included tonsill- ectomy, muscular fatigue, inoculation, and local infection, in particular of the tonsils and the intestines.Abortive cases of poliomyelitis showed a clinical non- specific illness resembling influenza, lasting fr*n two to seven days, with malaise, inconstant headache, shivering, mild fever, and a normal C.S.F.The non-paralytic form of the disease showed an extension of the infection to the central nervous system, characterized by muscular pains, stiffness of the back, and paraesthesiae, and accompanied by nystagmus, transitory muscular weakness, alteration in the deep reflexes, and changes in the C.S.F.The onset of paralysis, at times after a symptom-free interval, was accompanied by pain and hyperaesthesia.Variants of the paralytic form included ascending paralysis and the development of an acute myelitis.Polio-encephalitis was occasionally accompanied by mental symptoms, such as confusion or hypomania, and by drowsi- ness or more rarely coma.Involvement of the medulla might lead to defects in articulation, deglutition, respiration, and to circulatory failure.Dr. McAlpine concluded with a plea that for the control of epidemics of poliomyelitis emphasis should be shifted to the group of patients not showing paralysis.