Karen H. Lu, MD

https://openworks.mdanderson.org/legendsandlegacieschapters/1014/thumbnail.jp

Kinematic viscosity of therapeutic pulmonary surfactants with added polymers

AbstractThe addition of various polymers to pulmonary surfactants improves surface activity in experiments both in vitro and in vivo. Although the viscosity of surfactants has been investigated, the viscosity of surfactant polymer mixtures has not. In this study, we have measured the viscosities of Survanta and Infasurf with and without the addition of polyethylene glycol, dextran or hyaluronan. The measurements were carried out over a range of surfactant concentrations using two concentrations of polymers at two temperatures. Our results indicate that at lower surfactant concentrations, the addition of any polymers increased the viscosity. However, the addition of polyethylene glycol and dextran to surfactants at clinically used concentrations can substantially lower viscosity. Addition of hyaluronan at clinical surfactant concentrations slightly increased Infasurf viscosity and produced little change in Survanta viscosity. Effects of polymers on viscosity correlate with changes in size and distribution of surfactant aggregates and the apparent free volume of liquid as estimated by light microscopy. Aggregation of surfactant vesicles caused by polymers may therefore not only improve surface activity as previously shown, but may also affect viscosity in ways that could improve surfactant distribution in vivo

Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. <it>SULF1 </it>expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of <it>SULF1 </it>would impact clinicopathologic characteristics.</p> <p>Methods</p> <p>We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method.</p> <p>Results</p> <p>We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (<it>P </it>= 0.027; <it>P_trend</it>= 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (<it>P </it>= 0.013; <it>P_trend</it>= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (<it>P </it>= 0.014; <it>P_trend</it>= 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line.</p> <p>Conclusions</p> <p>These findings suggest that genetic variations in <it>SULF1 </it>may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of <it>SULF1 </it>SNPs are warranted.</p

Coordinated prophylactic surgical management for women with hereditary breast-ovarian cancer syndrome

<p>Abstract</p> <p>Background</p> <p>Women with <it>BRCA1 </it>or <it>BRCA2 </it>mutations have a substantially increased risk of breast and ovarian cancer compared with the general population. Therefore, prophylactic mastectomy (PM) and bilateral salpingo-oophorectomy (BSO) have been proposed as risk-reduction strategies for <it>BRCA1/2 </it>mutation carriers. We aimed to assess the feasibility of coordinated PM and BSO in hereditary breast-ovarian cancer syndrome.</p> <p>Methods</p> <p>High risk women for breast and ovarian cancer who underwent coordinated PM and BSO were included in this study. Clinical characteristics and surgical and oncologic outcomes were retrospectively reviewed.</p> <p>Results</p> <p>Twelve patients underwent coordinated PM and BSO. Ten had history of previous breast cancer. Autologous breast reconstruction was performed in ten patients. The mean age at surgery was 43 (range 34–65). Mean operating time was 9.3 hours (range 3–16) with a mean postoperative hospitalization of 5.4 days (range 4–8). Intraoperatively, there were no major surgical complications. Postoperatively, one patient developed an abdominal wound dehiscence, another reoperation for flap congestion; one had umbilical superficial epidermolysis, and one patient developed aspiration pneumonia. At a mean follow-up of 84 months, 10 of patients were cancer-free. Although no patients developed a new primary cancer, two developed a distant recurrence.</p> <p>Conclusion</p> <p>Coordinated PM and BSO is a feasible procedure with acceptable morbidity in selected high-risk patients that desire to undergo surgery at one operative setting.</p

Does TP53 increase the sensitivity of CA125 in early detection of ovarian cancer?

https://openworks.mdanderson.org/sumexp22/1149/thumbnail.jp

FATS is a transcriptional target of p53 and associated with antitumor activity

Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374) through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability

Impact of COVID-19 pandemic on chronic pain and opioid use in marginalized populations: A scoping review

IntroductionThe COVID-19 pandemic has had a variable effect on vulnerable populations, including patients with chronic pain who rely on opioid treatment or have comorbid opioid use disorder. Limited access to care due to isolation measures may lead to increased pain severity, worse mental health symptoms, and adverse opioid-related outcomes. This scoping review aimed to understand the impact of the COVID-19 pandemic on the dual epidemics of chronic pain and opioids in marginalized communities worldwide.MethodsSearches of primary databases including PubMed, Web of Science, Scopus, and PsycINFO were performed in March 2022, restricting the publication date to December 1, 2019. The search yielded 685 articles. After title and abstract screening, 526 records were screened by title and abstract, 87 through full-text review, of which 25 articles were included in the final analysis.ResultsOur findings illuminate the differential distribution of pain burden across marginalized groups and how it serves to heighten existing disparities. Service disruptions due to social distancing orders and infrastructural limitations prevented patients from receiving the care they needed, resulting in adverse psychological and physical health outcomes. Efforts to adapt to COVID-19 circumstances included modifications to opioid prescribing regulations and workflows and expanded telemedicine services.ConclusionResults have implications for the prevention and management of chronic pain and opioid use disorder, such as challenges in adopting telemedicine in low-resource settings and opportunities to strengthen public health and social care systems with a multidisciplinary and multidimensional approach

Diet, Weight Management, Physical activity and Ovarian & Breast Cancer Risk in Women With

INTRODUCTION: Women with pathogenic germline gene variants in METHODS: We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21. RESULTS: There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk. CONCLUSIONS: There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women wit

Energy Balance Related Lifestyle Factors and Risk of Endometrial and Colorectal Cancer among individuals With Lynch Syndrome: a Systematic Review

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to June 14th, 2018. In total, 1060 studies were identified and 16 were included. Three studies were related to EC and 13 to CRC. Overall, evidence suggests that weight status/weight change may not be associated with EC risk and multivitamin and folic-acid supplementation may be associated with decreased EC risk. Early-adulthood overweight/obese weight-status and adulthood weight-gain may be associated with increased CRC risk, whereas multivitamin supplementation, tea and high fruit intake, and physical activity may be associated with decreased CRC risk. Current evidence proposes that recommendations related to weight, some dietary habits, and physical activity recommended for the general public are also relevant to individuals with lynch syndrome. More research is needed, specifically prospective cohorts and randomized controlled trials, to determine if tailored recommendations are needed among individuals with lynch syndrome