tbuckley/cabot-search huggingface dataset:
Growth Factor Receptor Monoclonal Antibodies and Cancer Immunotherapy
Authors: G. H. Sato, J. D. Sato
Journal: JNCI Journal of the National Cancer Institute (1989)

With the description of the hybridoma technique by Kohler and Milstein (7), it became apparent that monoclonal antibodies were novel reagents with potential applications in the diagnosis and treatment of malignant diseases. It was hoped that the antigenic specificity intrinsic to these new immunological reagents could be translated into methods of attacking cancers with a degree of specificity not attainable by other modes of treatment. These hopes have remained largely unfulfilled owing to the great difficulty in identifying tumor-specific target antigens (2). However, despite the lack of absolute targeting specificity, advances have been made in the use of monoclonal antibodies as vehicles to deliver toxins, drugs, and radioisotopes to malignant cells. Clinical trials with monoclonal antibodies to tumor-associated antigens are under way (3). Malignancies of B and T cells are exceptions in that these cells produce unique antigens that are essential components of normal humoral arid cellular immune responses. Thus, the idiotypes of surface immunoglobulins and the variable regions of T-cell receptors are highly specific antigenic determinants on malignant lymphocytes, which can be exploited as targets for monoclonal antibodies. In perhaps the most impressive use of monoclonal antibodies to treat a human malignancy, a patient with a B-cell lymphoma went into complete clinical remission for 6 years following anti-idiotypic antibody therapy (4).
Publicity will highlight problem of obstetric fistula
Authors: Andrew Cole
Journal: BMJ (2006)

Hundreds of thousands of women in developing countries suffer the devastating injury during child bearing of obstetric fistula. But the agency behind a global campaign to eradicate the condition says it is simple to prevent and easy to treat.

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A woman attends the Addis Ababa fistula hospital, Ethiopia

Credit: P VIROT/WHO

The global campaign, led by the international development agency the United …

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Hello Out There…Is Anybody Listening?
Authors: Rosa Anna DeFilippis, Thea D. Tlsty
Journal: Cancer Discovery (2012)

Abstract Summary: Using a murine xenograft model system, Kuznetsov and colleagues show the existence of systemic interactions between a primary tumor and the growth of distal tumors in both homotypic and heterotypic tissues. Importantly, they show that the characteristics of the primary tumor govern the histologic features of the distal tumor through distinct pathways, thus providing novel opportunities for risk assessment, prognosis, prevention, and intervention. Cancer Discov; 2(12); 1084–6. ©2012 AACR. Commentary on Kuznetsov et al., p. 1150
QT interval prolongation and mortality in type 1 diabetic patients: a 5-year cohort prospective study. Neuropathy Study Group of the Italian Society of the Study of Diabetes, Piemonte Affiliate.
Authors: M Veglio, R Sivieri, A Chinaglia, L Scaglione, P Cavallo-Perin
Journal: Diabetes Care (2000)

OBJECTIVE: The aim of the study was to assess the relationship between QT interval prolongation and mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Data on survival after 5 years were obtained from 316 of 379 patients (83.3%) who took part in a study on the prevalence of diabetic neuropathy and QT interval prolongation. RESULTS: Mortality at 5 years was 6.32%. Patients who survived were significantly younger (P = 0.04), had a shorter duration of diabetes (P = 0.01), had lower systolic (P = 0.004) and diastolic (P = 0.03) blood pressure levels, and had a shorter QT interval corrected for the previous cardiac cycle length (QTc) (P = 0.000005) than subjects who died. In univariate analysis, patients had a higher risk of dying if they had a prolonged QTc (odds ratio [OR] 20.14 [95% CI 5.7-70.81) or if they were affected by autonomic neuropathy (3.55 [1.4-8.9]). QTc prolongation was the only variable that showed a significant mortality OR in multivariate analysis (24.6 [6.51-92.85]; P = 0.0000004). CONCLUSIONS: This is the first cohort-based prospective study indicating that QTc prolongation is predictive of increased mortality in type 1 diabetic patients.
Dendritic Cell-Tumor Fusion Vaccines for Renal Cell Carcinoma
Authors: David Avigan
Journal: Clinical Cancer Research (2004)

Abstract Renal cell carcinoma is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. A promising area of investigation is the use of cancer vaccines to educate host immunity to specifically target and eliminate malignant cells. Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely effective in generating primary immune responses. DCs that are manipulated to present tumor antigens induce antitumor immunity in animal models and preclinical human studies. A myriad of strategies have been developed to effectively load tumor antigen onto DCs, including the introduction of individual peptides, proteins, or tumor-specific genes, as well as the use of whole tumor cells as a source of antigen. A promising approach for the design of cancer vaccines involves the fusion of whole tumor cells with DCs. The DC-tumor fusion presents a spectrum of tumor-associated antigens to helper and cytotoxic T-cell populations in the context of DC-mediated costimulatory signals. In animal models, vaccination with DC-tumor fusions resulted in protection from tumor challenge and regression of established metastatic disease. We have conducted phase 1 dose escalation studies in which patients with metastatic breast and renal cancer underwent vaccination with DC-tumor fusions. Twenty-three patients underwent vaccination with autologous DC-tumor fusions. Vaccination was well tolerated without substantial treatment-related toxic effects. Immunologic responses and disease regression were observed in a subset of patients. Future studies will explore the effect of DC maturation and cytokine adjuvants on vaccine potency.
Factors influencing progression of renal failure in autosomal dominant polycystic kidney disease.
Authors: G Choukroun, Y Itakura, G Albouze, J L Christophe, N K Man, J P Grünfeld, P Jungers
Journal: Journal of the American Society of Nephrology (1995)

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.
The American-European consensus conference on ARDS, Part 2
Authors: A. Artigas, G. R. Bernard, J. Carlet, D. Dreyfuss, L. Gattinoni, L. Hudson, M. Lamy, J. J. Marini, M. A. Matthay, M. R. Pinsky, R. Spragg, P. M. Suter
Journal: Intensive Care Medicine (1998)
The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma
Authors: R Polosa, CK Lai, C Robinson, ST Holgate
Journal: European Respiratory Journal (1990)

Bradykinin is a naturally occurring nonapeptide which may contribute to the pathogenesis of bronchial asthma. When inhaled by asthmatic subjects it is a potent bronchoconstrictor, but with repeated challenge airways responsiveness to the peptide decreases markedly. In vitro studies suggest that loss of bradykinin responsiveness may be due to the secondary generation of relaxant prostanoids. We have used the potent cyclooxygenase inhibitor flurbiprofen to investigate the potential role of prostanoid generation in bradykinin tachyphylaxis in eight asthmatic patients. The effects of oral flurbiprofen (150 mg) and matched placebo were observed on two consecutive dose response studies with inhaled bradykinin and histamine in a double-blind, randomized study. Venous blood was taken to measure the serum concentration of thromboxane B2 (TxB2) as a check on the extent of cyclooxygenase blockade achieved by flurbiprofen. Following recovery from the first challenge with bradykinin, the asthmatic airways showed a reduced response to a second challenge with this nonapeptide, the provocative concentration producing a 20% fall from baseline (PC20) increasing from 0.07 to 0.42 mg.ml-1 (p less than 0.01). The airway response to inhaled histamine after the second bradykinin challenge was not significantly changed. In the presence of demonstrable cyclooxygenase inhibition, flurbiprofen failed to prevent the development of reduced responsiveness to bradykinin observed on the second challenge, the PC20 increasing from 0.10 to 0.48 mg.ml-1 (p less than 0.01). This study demonstrates that repeated exposure to inhaled bradykinin results in loss of the bronchoconstrictor response which appears specific for this agonist and not secondary to the increased generation of protective prostanoids.
Role of Radiotherapy in the Treatment of Supratentorial Primitive Neuroectodermal Tumors in Childhood: Results of the Prospective German Brain Tumor Trials HIT 88/89 and 91
Authors: B. Timmermann
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.
AN OBSERVATION ON THE TREATMENT OF MENTAL CASES WITH SUB-SHOCK DOSES OF INSULIN
Authors: C. R. BENNETT, T. K. MILLER
Journal: American Journal of Psychiatry (1940)

1. We have observed, in the past year and a half, among a mixed population of over 2400 patients, that a course of sub-shock doses of insulin is effective in controlling most of the problems of management of uncooperative mental patients. 2. The necessity of sedation by drugs can be limited to epileptics and emergency nocturnal disturbances. 3. Difficult feeding cases can be largely corrected by the use of sub-shock doses of insulin. 4. Sub-shock doses of insulin are effective in all types of cases where there are no physical contraindications. 5. No special equipment or personnel is necessary to carry out this form of therapy. 6. Sub-shock insulin therapy is effective in aborting caruncles, carbuncles and acne simplex, as well as in producing more rapid healing in the well-developed lesion. 7. Sub-shock insulin therapy is in no sense considered a curative therapy although many favorable remissions occur. 8. There is need for further controlled study of this type of therapy.
Inflammatory bowel disease therapies and cancer risk: where are we and where are we going?
Authors: Laurent Beaugerie
Journal: Gut (2011)

Although there has been a recent trend towards a decreased absolute age-standardised mortality from cancer in Europe,1 in 2004, for the first time, cancer became the main cause of death in the general population in France.2 This apparent paradox is explained by a faster improvement of the prognosis of non-cancer diseases. Cancer risk has therefore become a lifelong major fear for gastroenterologists and patients when considering the long-term impact of the natural history and treatment of inflammatory bowel diseases (IBDs).

Life expectancy is normal for patients with ulcerative colitis (UC), with no excess mortality from cancer in population-based studies.3 For patients with Crohn's disease (CD), life expectancy is slightly reduced.4 A significant increase in deaths from cancer was reported in the most recent meta-analysis of population-based studies,4 but this was probably due to an over-representation of smoking-related causes of death in a disease where smokers are over-represented. In a Californian medico-administrative database, no overall excess mortality from cancer was demonstrated in either type of IBD, irrespective of the treatments used.5 This reassuring general background must be highlighted before discussion of the specific details of inflammation and immunosuppression-related cancers in IBD.

There is no evidence for a common genetic background between IBD and a susceptibility to cancer. For environmental factors, increased and decreased proportions of smokers in CD and UC compared with the general population are associated with corresponding variations in the incidence of lung and urinary bladder cancers.6 Finally, immunosuppression and inflammation are the two main drivers of IBD-related carcinogenesis. The difficulty is that these two mechanisms may be interlinked, particularly in the intestinal tissues; thus, we will now distinguish the true (negative and positive) effects of IBD treatments.

We have learnt …
Acute lung injury after aortic surgery: the relation between lung and leg microvascular permeability to 111indium-labelled transferrin and circulating mediators.
Authors: P G Raijmakers, A B Groeneveld, J A Rauwerda, G J Teule, C E Hack
Journal: Thorax (1997)

BACKGROUND: Aortic surgery is a risk factor for acute lung injury and this may relate to ischaemia/reperfusion (I/R) of the lower body and release of inflammatory mediators. The aim of this study was to define the changes in microvascular protein permeability and circulating inflammatory mediators after aortic surgery. METHODS: In 11 consecutive patients who underwent elective aortic surgery microvascular permeability in lung and leg was measured before and a median of 2.8 hours after completion of surgery using 111indium (In)-labelled transferrin and 99mtechnetium (Tc)-labelled red blood cells, yielding a protein leak index (PLI) that is specific for protein permeability. Circulating leucocyte counts and levels of inflammatory mediators were determined. RESULTS: In the lung the PLI rose from a median of 0.6 (range -0.5 to 2.2) x 10(-3)/min before surgery to 5.4 (-2.3 to 33.5) x 10(-3)/min after surgery, and in the leg from 0.3 (-1.6 to 1.7) x 10(-3)/min to 5.0 (1.0 to 27.8) x 10(-3)/min. The increase in PLI in the lung was related to that in the leg. Levels of activated complement C3a and tumour necrosis factor-alpha did not change, but levels of interleukin (IL)-6, IL-8 and elastase-alpha 1-antitrypsin increased. After surgery there was slight neutrophilia and the leucocyte counts were inversely related to the IL-8 level. The rise in lung but not in leg PLI was greatest in patients with the highest IL-8 levels and the lowest leucocyte counts. CONCLUSIONS: Early after aortic surgery microvascular protein permeability increases in the leg and lung. Leg I/R injury may result in neutrophil activation and release of IL-8, which may induce neutrophil sequestration and subsequently increased pulmonary microvascular permeability. These findings may help to explain the occurrence of acute lung injury after I/R in man.
CYCLOSPORIN A INITIALLY AS THE ONLY IMMUNOSUPPRESSANT IN 34 RECIPIENTS OF CADAVERIC ORGANS: 32 KIDNEYS, 2 PANCREASES, AND 2 LIVERS
Authors: R.Y. Calne, K. Rolles, S. Thiru, P. Mcmaster, G.N. Craddock, S. Aziz, D.J.G. White, D.B. Evans, D.C. Dunn, R.G. Henderson, P. Lewis
Journal: The Lancet (1979)
Altered MicroRNA Expression in Cervical Carcinomas
Authors: Jeong-Won Lee, Chel Hun Choi, Jung-Joo Choi, Young-Ae Park, Seung-Jun Kim, Seung Yong Hwang, Woo Young Kim, Tae-Joong Kim, Je-Ho Lee, Byoung-Gie Kim, Duk-Soo Bae
Journal: Clinical Cancer Research (2008)

Abstract Purpose: MicroRNAs (miRNA) are small noncoding RNAs that are 18 to 25 nucleotides in length; they regulate the stability or translational efficiency of target mRNAs. Emerging evidence suggests that miRNAs might be involved in the pathogenesis of a variety of human cancers. Experimental Design: In this study, we profiled miRNA expression in 10 early stage invasive squamous cell carcinomas (ISCC) and 10 normal cervical squamous epithelial specimens using TaqMan real-time quantitative PCR array methods. In order to evaluate the role of miR-199a, one of the most significantly overexpressed in ISCCs, we transfected cervical cancer cells (SiHa and ME-180) with anti–miR-199a oligonucleotides and assessed the cell viability. Results: We found 70 genes (68 up-regulated, 2 down-regulated) with significantly different expression in the ISCCs compared with normal samples (P &amp;lt; 0.05). When we analyzed the expression of the 10 most significant miRNAs in 31 ISCCs, increased miR-127 expression was significantly associated with lymph node metastasis (P = 0.006). Transfection of anti–miR-199a oligonucleotides to cervical cancer cells suppressed cell growth in vitro, which was potentiated with the anticancer agent cisplatin. Conclusions: Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, they may offer new candidate targets to be exploited for both prognostic and therapeutic strategies in patients with cervical cancer.
Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures.
Authors: J A Lorenzo, J Quinton, S Sousa, L G Raisz
Journal: Journal of Clinical Investigation (1986)

We examined two inhibitors of DNA synthesis, hydroxyurea (HU) and aphidicholin (APC), and two inhibitors of prostaglandin cyclooxygenase, indomethacin and flufenamic acid, for their effects on the resorptive responses of fetal rat long-bone cultures to epidermal growth factor (EGF) and parathyroid hormone (PTH). As we have previously found, HU decreased unstimulated 45Ca release but had little effect on the resorptive response to PTH. HU also did not block resorption stimulated by EGF. Addition of the cyclooxygenase inhibitor, indomethacin, did not alter the resorptive responses of unstimulated or PTH-treated cultures in either the presence or absence of HU or the resorptive response of bones cultured with EGF alone. However, indomethacin completely blocked the resorptive response to EGF of bones that were cultured with HU. The effects of indomethacin on EGF-mediated resorption in HU-treated cultures appeared to be related to an inhibition of prostaglandin synthesis since flufenamic acid had similar effects. However, the effects of HU on the resorptive response to EGF may not have resulted solely from its inhibitory action on DNA synthesis since APC, in the absence of cyclooxygenase inhibitors, completely blocked EGF-mediated resorption without significantly affecting the response to PTH. These results demonstrate that the mechanisms regulating PTH- and EGF-mediated resorption in fetal rat long-bone cultures differ, and imply that a component of EGF-mediated resorption in these cultures is dependent on sustained DNA synthesis.
Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients
Authors: Mehdi Khellaf, Anaïs Charles-Nelson, Olivier Fain, Louis Terriou, Jean-François Viallard, Stéphane Cheze, Julie Graveleau, Borhane Slama, Sylvain Audia, Mikael Ebbo, Guillaume Le Guenno, Manuel Cliquennois, Gilles Salles, Caroline Bonmati, France Teillet, Lionel Galicier, Arnaud Hot, Olivier Lambotte, François Lefrère, Salimatou Sacko, Dieudonné Kilendo Kengue, Philippe Bierling, Françoise Roudot-Thoraval, Marc Michel, Bertrand Godeau
Journal: Blood (2014)