115 research outputs found
No Evidence of HIV and SIV Sequences in Two Separate Lots of Polio Vaccines Used in the First U.S. Polio Vaccine Campaign
AbstractWe obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present
Adapting to 4 Degrees C World
The Paris Agreement\u27s goal to hold warming to 1.50-2 0 C above pre-industrial levels now appears unrealistic. Profs. Robin Kundis Craig and J.B. Ruhl have recently argued that because a 40 C world may be likely, we must recognize the disruptive consequences of such a world and respond by reimagining governance structures to meet the challenges of adapting to it. In this latest in a biannual series of essays, they and other members of the Environmental Law Collaborative explore what 40 C might mean for a variety of current legal doctrines, planning policies, governance structures, and institutions
A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation
Nanoparticles introduced in living cells are capable of strongly promoting
the aggregation of peptides and proteins. We use here molecular dynamics
simulations to characterise in detail the process by which nanoparticle
surfaces catalyse the self- assembly of peptides into fibrillar structures. The
simulation of a system of hundreds of peptides over the millisecond timescale
enables us to show that the mechanism of aggregation involves a first phase in
which small structurally disordered oligomers assemble onto the nanoparticle
and a second phase in which they evolve into highly ordered beta-sheets as
their size increases
Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma
Germline BAP1 mutations predispose to several cancers, in particular malignant
mesothelioma. Mesothelioma is an aggressive malignancy generally associated
to professional exposure to asbestos. However, to date we found that none of the
mesothelioma patients carrying germline BAP1 mutations were professionally
exposed to asbestos. We hypothesized that germline BAP1 mutations might
influence the asbestos-induced inflammatory response that is linked to asbestos
carcinogenesis, thereby increasing the risk of developing mesothelioma after
minimal exposure. Using a BAP1+/- mouse model, we found that, compared to
their wild type littermates, BAP1+/- mice exposed to low-dose asbestos fibers
showed significant alterations of the peritoneal inflammatory response, including
significantly higher levels of pro-tumorigenic alternatively polarized M2
macrophages, and lower levels of several chemokines and cytokines. Consistent
with these data, BAP1+/- mice had a significantly higher incidence of
mesothelioma after exposure to very low doses of asbestos, doses that rarely
induced mesothelioma in wild type mice. Our findings suggest that minimal
exposure to carcinogenic fibers may significantly increase the risk of malignant
mesothelioma in genetically predisposed individuals carrying germline BAP1
mutations, possibly via alterations of the inflammatory response
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The LIN28B/let-7 axis is a novel therapeutic pathway in Multiple Myeloma
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof-of-principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC dependent cancers as well
European Code against Cancer 4th Edition:Breastfeeding and cancer
Breast cancer is the most frequent cancer in women, and incidence rates have been rising in European Union (EU) countries over recent decades due in part to a sharp decline in breastfeeding practices. Evidence for a protective association between breastfeeding and the risk of breast cancer at all ages is convincing, and modest protective relationships between breastfeeding and the risk of endometrial and ovarian cancers have been suggested. The reduction in breast cancer risk is estimated at 2% for an increase of 5 months of lifetime breastfeeding. The longer women breastfeed, the more they are protected against breast cancer. In addition, breastfeeding is associated with several health benefits for both the mother and the breastfed child. Taking all this evidence into account, the 4th edition of the European Code against Cancer recommends: ââBreastfeeding reduces the motherâs cancer risk. If you can, breastfeed your babyââ
European Code against Cancer 4th Edition: Alcohol drinking and cancer.
Alcohol consumption is the third leading risk factor for disease and mortality in Europe. As evaluated by the International Agency for Research on Cancer (IARC) Monographs, a causal relationship is established for consumption of alcoholic beverages and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum and female breast, even at low and moderate alcohol intakes. The higher the amount of alcohol consumed, the higher the risk of developing cancer. In Europe, an estimated 10% (95% CI: 7%-13%) of all cancer cases in men and 3% (95% CI: 1%-5%) of all cancer cases in women are attributable to alcohol consumption. Several biological mechanisms explain the carcinogenicity of alcohol; among them, ethanol and its genotoxic metabolite, acetaldehyde, play a major role. Taking all this evidence into account, a recommendation of the 4th edition of European Code against Cancer is: "If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention.
European Code against Cancer 4th Edition:Obesity, body fatness and cancer
AbstractIt is estimated that over half the population of the European Union (EU) is overweight or obese due to an imbalance between energy expenditure and energy intake; this is related to an obesogenic environment of sociocultural, economic and marketing challenges to the control of body weight. Excess body fat is associated with nine cancer sites â oesophagus, colorectum, gall bladder, pancreas, postmenopausal breast, endometrium, ovary, kidney and prostate (advanced) â and 4â38% of these cancers (depending on site and gender) can be attributed to overweight/obesity status. Metabolic alterations which accompany excess body weight are accompanied by increased levels of inflammation, insulin, oestrogens and other hormonal factors. There are some indications that intentional weight loss is associated with reduced cancer incidence (notably in postmenopausal breast and endometrial cancers). Excess body weight is also a risk factor for several other diseases, including diabetes and heart disease, and is related to higher risk of premature death.In reviewing the current evidence related to excess body fat and cancer, the European Code against Cancer Nutrition Working Group has developed the following recommendation: âTake action to be a healthy body weightâ
European Code against Cancer 4th Edition:Diet and cancer
AbstractLifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer.Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt
Changes in breast density and circulating estrogens in postmenopausal women receiving adjuvant anastrozole
Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes
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