Approach For Cancer Prevention Research Articles

Intestinal microbiota and colorectal cancer: changes in the intestinal microenvironment and their relation to the disease.

Tools that predict the risk of colorectal cancer are important for early diagnosis, given the high mortality rate for this cancer. The composition of the intestinal microbiota is now considered to be a risk factor for the development of colorectal cancer. This discovery has motivated a growing number of studies to identify the micro-organisms responsible for the onset and/or progression of colorectal cancer. With this in mind, this review discusses the relationship between the composition of the intestinal microbiota and colorectal cancer risk. Prospective and case-control studies indicate that the intestinal microbiota of individuals with colorectal cancer usually contains a greater proportion of bacteria responsible for gastrointestinal tract inflammatory diseases, as well as bacteria that produce toxins and carcinogenic metabolites. In contrast, there tends to be a reduced presence of butyric acid-producing bacteria, probiotic bacteria and potentially probiotic bacteria. Despite these differences, the onset and development of colorectal cancer cannot be attributed to a specific micro-organism. Thus, studies focused on the formation of the intestinal microbiota and factors that modulate its composition are important for the development of approaches for colorectal cancer prevention.

Cancer control in the Pacific: big challenges facing small island states.

This Series paper describes the current state of cancer control in Pacific island countries and territories (PICTs). PICTs are diverse but face common challenges of having small, geographically dispersed, isolated populations, with restricted resources, fragile ecological and economic systems, and overburdened health services. PICTs face a triple burden of infection-related cancers, rapid transition to lifestyle-related diseases, and ageing populations; additionally, PICTs are increasingly having to respond to natural disasters associated with climate change. In the Pacific region, cancer surveillance systems are generally weaker than those in high-income countries, and patients often present at advanced cancer stage. Many PICTs are unable to provide comprehensive cancer services, with some patients receiving cancer care in other countries where resources allow. Many PICTs do not have, or have poorly developed, cancer screening, pathology, oncology, surgical, and palliative care services, although some examples of innovative cancer planning, prevention, and treatment approaches have been developed in the region. To improve cancer outcomes, we recommend prioritising regional collaborative approaches, enhancing cervical cancer prevention, improving cancer surveillance and palliative care services, and developing targeted treatment capacity in the region.

Somatic genome alterations in relation to age in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common cause of global cancer-related mortality and the major risk factor is smoking consumption. By analyzing 486 LUAD samples from The Cancer Genome Atlas, we detected a higher mutational burden among younger patients in the global cohort as well as in the TP53-mutated subcohort. The interaction effect of patient age and TP53 mutations significantly affected the mutational rate of younger TP53-mutated patients. Furthermore, we detected a significant enrichment of the smoking-related signature SI4 (SI4) among younger TP53-mutated patients, meanwhile the age-related Signature 1 (SI1) significantly increased in proportion to patient age. Although present and past smoking is reported in the TP53 wild-type patients, we observed a lower average number of somatic mutations, with no correlation with patient age. Overall, TP53 mutations were significantly higher in younger patients and mainly characterized by SI4 and Signature 24 (SI24). Therefore, TP53 seemed to acquire a particular sensitivity to smoking related C>A mutations in younger patients. We hypothesize that TP53 mutations at a younger age might be a crucial factor enhancing the sensitivity to smoking-related mutations leading to a burst of somatic alterations. The mutational profile of cancer cell might reflect the mutational processes operative in aging in a given tissue. Therefore, TP53-mutated and TP53 wild-type patient groups might represent phenotypes which endure aging-related mutational processes with different strength. Our study provides indications of age-dependent differences in mutational backgrounds that might be relevant for cancer prevention and age-adjusted treatment approaches.

AKT as a Therapeutic Target for Cancer.

Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositide-dependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen synthase kinase 3 beta (GSK3β), or forkhead box protein O1 (FOXO1). The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy. In this review, we discuss the rationale for targeting AKT and also provide details regarding synthetic and natural AKT-targeting compounds and their associated studies.

Role of cytoplasmic lncRNAs in regulating cancer signaling pathways.

Cancer remains a serious healthcare problem despite significant improvements in early detection and treatment approaches in the past few decades. Novel biomarkers for diagnosis and therapeutic strategies are urgently needed. In recent years, long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in tumors and show crosstalk with key cancer-related signaling pathways. In this review, we summarized the current progress of research on cytoplasmic lncRNAs and their roles in regulating cancer signaling and tumor progression, further characterization of which may lead to effective approaches for cancer prevention and therapy.

Dietary supplementation with procyanidin-rich Pinus pinaster extract is associated with attenuated Ehrlich tumor development in mice

Inflammation and oxidative stress are related to cancer initiation and progression. We hypothesized that dietary supplementation with a procyanidin-rich Pinus pinaster extract (Pyc) with known antioxidant and anti-inflammatory effects could induce systemic protection, thereby attenuating tumor development. To test our hypothesis, mice were subjected to long-term supplementation (20 days, every 24 h) with saline, 25 mg/kg resveratrol or 100 mg/kg Pyc. Pyc was administered at a maximum tolerated oral dose, previously determined using toxicity indicators. Ten days after Ehrlich ascites tumor induction, weight gain and abdominal circumference increase were calculated. Ascitic fluid from six mice/group was evaluated by determining total volume; tumor packed cell volume; cell viability; tumor cell death type; inflammatory infiltrate; and levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), carbonyl proteins, lipid peroxidation, cyclooxigenase-2 (COX-2) expression and Akt phosphorylation (p-Akt). Ten mice/group were monitored to evaluate survival. Pyc and resveratrol were associated with reduced weight gain (>30%), abdominal circumference and ascitic volume. Tumor packed cell volume was reduced in Pyc-supplemented mice (26%), which had the largest tumor cell count reduction (>35%), increased ascitic fluid apoptosis rates (20%) and the longest survival (>2-fold). Pyc and resveratrol treatment both reduced inflammatory infiltrate and levels of TNF-α, IL-1β, carbonyl proteins, lipid peroxidation (~ 30%) and p-Akt (up to 4-fold). Only Pyc significantly inhibited COX-2. Pyc attenuated oxidative and inflammation mediators and impaired tumor development, supporting our hypothesis and suggesting Pyc as a candidate for future studies in multitargeted dietary-based cancer prevention approaches.

Capacity Building for and Implementation of Policy, Systems, and Environmental Change: Results from a Survey of the National Comprehensive Cancer Control Program.

Policy, systems, and environmental (PSE) approaches are commonly used to improve population health. Cancer-related examples include providing data and education to stakeholders about policies that support healthy living, or health systems changes such as universal reminders about recommended cancer screening. The National Comprehensive Cancer Control Program (NCCCP) funds health departments to form cancer coalitions that develop and implement cancer plans. NCCCP initiated a demonstration program in 13 of 65 funded grantees to determine whether skilled, dedicated staffing and using a strategic process to examine data, form a workgroup, and develop an agenda would enhance their capacity to implement PSE approaches, recruit new partners, and provide data and education to stakeholders. The objective of this study was to compare demonstration program grantees to other NCCCP grantees on their ability to develop and implement PSE strategies, and the short-term results that were achieved. Program directors (PDs) from each NCCCP-funded jurisdiction completed web surveys at 2 time points during implementation to assess changes in their capacity for PSE approaches, identify implementation activities, and document short-term outcomes. Responses from demonstration program PDs and other PDs at both time points were compared in a descriptive analysis. Demonstration program grantees experienced greater increases in skills and capacity to address PSE approaches, engaged in necessary implementation activities more often, and achieved greater improvements in stakeholder and decision maker awareness and support for PSE strategies, compared to nonparticipating NCCCP grantees. These findings support continued implementation of PSE approaches for sustainable cancer prevention and control.

Update of: Ouedraogo et al., Expanding the Single-Visit Approach for Cervical Cancer Prevention: Successes and Lessons From Burkina Faso.

Update of: Ouedraogo et al., Expanding the Single-Visit Approach for Cervical Cancer Prevention: Successes and Lessons From Burkina Faso.

Lessons Learned From Canada in Working Together to Support Indigenous Health and Wellness

Background and context: First Nations, Inuit and Métis bear a disproportionate burden of cancer in Canada. In the spirit of truth and reconciliation, and to have the greatest impact, it is important for nonindigenous and indigenous partners to work together, and reflect on lessons learned in collaborating, to support First Nations, Inuit and Métis health and wellness. Aim: In response to the national Truth and Reconciliation Commission Calls to Action, the Canadian Partnership Against Cancer committed to understanding how collaborative projects funded through the Coalitions Linking Action and Science for Prevention (CLASP) initiative were successful in bringing together diverse groups - both indigenous and nonindigenous - to create and apply culturally-relevant cancer prevention approaches. Strategy/Tactics: Seven projects funded through the CLASP initiative, from 2009 to 2016, brought together over 275 First Nations, Inuit, or Métis communities, schools, and organizations with government, nongovernment, and academic partners in collaborative coalitions. The projects addressed cancer prevention issues prioritized by First Nations, Inuit, and Métis (e.g., unhealthy eating and physical inactivity) through approaches that were holistic and culturally-relevant, such as utilizing intergenerational knowledge sharing, incorporating mental wellness, and supporting existing capacity within communities. Program/Policy process: Over 30 knowledge products developed by the projects were reviewed to identify preliminary lessons learned about partner collaboration. Preliminary lessons learned were verified and expanded upon through nine key informant interviews with CLASP partners. Key informant interviews were informed by four advisors representing indigenous and nonindigenous leaders and partners. The refined set of lessons learned were finalized through qualitative analysis and validated through a conference session and one-day workshop with CLASP partners and First Nations, Inuit, and Métis community leaders. Outcomes: Twenty-seven lessons learned that describe how nonindigenous and First Nations, Inuit and Métis CLASP partners worked together to develop and put into practice culturally-appropriate cancer prevention approaches were identified. The lessons learned were grouped into six themes: 1. respectful relationships; 2. engagement with indigenous communities; 3. addressing accountability requirements, decision-making, and governance; 4. community direction; 5. supports and resources; 6. communication and knowledge exchange. What was learned: The actionable lessons learned are intended to guide future relationship building and engagement between nonindigenous partners and First Nations, Inuit and Métis partners. It is intended that these lessons will be beneficial to collaborative cancer prevention efforts around the world and inform broader system change leading to a reduction in indigenous cancer burden disparities.

Application of the Adverse Outcome Pathway Framework to Risk Assessment for Predicting Carcinogenicity of Chemicals.

As industry develops in modern society, many chemicals are being used. The safety of chemicals is an important issue because humans are constantly exposed to chemicals throughout their daily life. Through a risk assessment, the hazardous human effects of chemicals can be identified. Recently, the adverse outcome pathway (AOP) framework has been used to predict the adverse effects of chemicals. As a conceptual framework for organizing existing biological knowledge, the AOP consists of a molecular initiating event, key events, and an adverse outcome. These independent elements represent biological responses and are connected by key event relationships. This AOP framework provides intuitive hazard identification that can be helpful for carcinogenic risk assessment of chemicals. In this review, we introduce the application of the AOP framework to risk assessment for predicting carcinogenicity of chemicals and illustrate the utility of this approach for cancer prevention.

Molecular Pathology of High-Grade Prostatic Intraepithelial Neoplasia: Challenges and Opportunities.

A better understanding of the early stages of prostate cancer initiation, potentially arising from precursor lesions, may fuel development of powerful approaches for prostate cancer prevention or interception. The best-known candidate for such a precursor lesion has been referred to as high-grade prostatic intraepithelial neoplasia (HGPIN). Although there is significant evidence supporting the notion that such HGPIN lesions can give rise to invasive adenocarcinomas of the prostate, there are also numerous complicating considerations and evidence that cloud the picture in many instances. Notably, recent evidence has suggested that some fraction of such lesions that are morphologically consistent with HGPIN may actually be invasive carcinomas masquerading as HGPIN-a state that we term "postinvasive intraepithelial carcinoma" (PIC). Although the prevalence of such PIC lesions is not fully understood, this and other factors can confound the potential of identifying prostate precursors that can be targeted for disease prevention, interception, or treatment. Here, we review our current understanding of the morphological and molecular pathological features of prostate cancer precursor lesions.

Abstract C91: Exploring the role of social determinants on HPV vaccine intentions and uptake among ethnoracial minority college students

Abstract Background: HPV-related diseases and cancers disproportionately affect low-income and ethnoracial minorities. HPV vaccines have the potential to reduce ethnoracial disparities in HPV-related diseases and cancers; however, HPV vaccine uptake has remained sub optimal. To achieve the greatest impact, public health campaigns should focus on improving HPV vaccine coverage where it is weakest. They should also explore more subtle but potentially significant determinants of HPV vaccine initiation and completion. The social determinants of health approach may be useful in explaining the disparities in HPV vaccine uptake rates. Methods: Ethnoracial minority male and female college students (n=956) recruited from a large public university in the southeast US completed a 20-minute web-based survey in the fall of 2011. Survey items were adapted from previous research of psychosocial HPV studies among men and women, and were based on constructs from the Health Belief Model and Social Cognitive Theory. This analysis examined self-reported data on participants' sociodemographics, HPV knowledge, HPV vaccine status, intent to receive HPV vaccination, and the importance of health provider recommendation for the HPV vaccine. Univariate analyses examined the sample distribution; bivariate analyses were conducted to examine the relationship between sociodemographics and HPV knowledge, intent, and importance of provider recommendation; and multinomial logistic regression analysis examined associations between the importance of a provider to recommend the HPV vaccine and HPV-related variables previously listed in the bivariate analysis. Results: The mean age of the sample was 23.6 years (SD=6.629) years. The sample was mostly women (74.4%), Hispanic or Latino/a (46.3%), not married (75.4%), insured (76.9%), and completed 2 years or less of college (41.9%). Frequency distributions indicated that 88.5% reported that they were knowledgeable about HPV, 79.7% reported that they were knowledgeable about the HPV vaccine, and 62.1% had a place where they could receive the vaccination. In addition, 29.6% of the sample reported receiving at least 1 dose while 22.7% of the sample reported that they intend to get the HPV vaccine. Bivariate analyses showed that participants most likely to have previous HPV knowledge were women (91.8%; p < 0.001) and participants with an undergraduate or graduate degree (92.2%; p = 0.036). Participants who were most likely to have previous HPV vaccine knowledge were most likely to be women (86.8%; p < 0.001), possess an undergraduate or graduate degree (88.7%; p=0.001), and married (87.7%; p < 0.001). Participants who reported having received at least one dose were more likely to be women (37.7%; p <0.001), have completed 2 years of college or less (35.7%; p <0.001), and not married (31.8%; p=0.01). Those who had 2 years of college or less (27.9%; p<0.001) and not married (25.2%; p=0.01) were more likely to intend to get the HPV vaccination compared to participants with more education and married, respectively. Participants who indicated that the importance for a health care provider to recommend the HPV vaccine was very important were most likely to have 2 years of college or less (52.9%; p=0.02).Multinomial logistic regression analysis showed that participants who do not believe that the provider recommendation is important or somewhat important were less likely to have received a dose of the vaccine (p<0.001), and less likely to have a place to receive the vaccination (p=.008; p=.003, respectively). Conclusions: As ethnoracial minorities continue to grow in the United States over the next several decades, it is imperative that we not only improve HPV vaccination rates overall, but also focus on high-risk populations to prevent HPV-related disparities. Taking a social determinants of health approach in HPV-related disease and cancer prevention will be necessary to achieve equity and eliminate HPV-related disparities. Citation Format: Natalie D. Hernandez, Dexter Cooper, Stephanie Kolar, Christopher Wheldon. Exploring the role of social determinants on HPV vaccine intentions and uptake among ethnoracial minority college students [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C91.

Precision Prevention and Early Detection of Cancer: Fundamental Principles.

Prevention and early detection is critical for reducing the population cancer burden. Two approaches have been used: Population approaches change social norms (e.g., smoking bans) or impose incentives (e.g., cigarette taxes); high-risk strategies intervene upon individuals with elevated cancer risk (e.g., smoking cessation). Knowledge about carcinogenesis mechanisms, extreme exposures, and inherited susceptibility provides opportunities to develop precision prevention and early-detection (PPED) strategies. PPED aims to understand the basis of risk, identify groups that optimally benefit from interventions, characterize heterogeneity in intervention responses, optimize intervention timing, and minimize toxicities. We propose a framework around which PPED strategies can be developed. Currently available cancer prevention and early-detection approaches have the potential to reduce a large proportion of the cancer burden in the population. However, even if fully implemented, existing methods cannot fully eliminate the cancer burden. New PPED approaches that exploit the growing knowledge of molecular and biological cancer mechanisms should be developed and implemented. Cancer Discov; 8(7); 803-11. ©2018 AACR.

Expanding the Single-Visit Approach for Cervical Cancer Prevention: Successes and Lessons From Burkina Faso.

Cervical cancer accounts for 23% of cancer incidence and 22% of cancer mortality among women in Burkina Faso. These proportions are more than 2 and 5 times higher than those of developed countries, respectively. Before 2010, cervical cancer prevention (CECAP) services in Burkina Faso were limited to temporary screening campaigns. Between September 2010 and August 2014, program implementers collaborated with the Ministry of Health and professional associations to implement a CECAP program focused on coupling visual inspection with acetic acid (VIA) for screening with same-day cryotherapy treatment for eligible women in 14 facilities. Women with larger lesions or lesions suspect for cancer were referred for loop electrosurgical excision procedure (LEEP). The program trained providers, raised awareness through demand generation activities, and strengthened monitoring capacity. Data on program activities, service provision, and programmatic lessons were analyzed. Three data collection tools, an individual client form, a client registry, and a monthly summary sheet, were used to track 3 key CECAP service indicators: number of women screened using VIA, proportion of women who screened VIA positive, and proportion of women screening VIA positive who received same-day cryotherapy. Over 4 years, the program screened 13,999 women for cervical cancer using VIA; 8.9% screened positive; and 65.9% received cryotherapy in a single visit. The proportion receiving cryotherapy on the same day started at a high of 82% to 93% when services were provided free of charge, but dropped to 51% when a user fee of $10 was applied to cover the cost of supplies. After reducing the fee to $4 in November 2012, the proportion increased again to 78%. Implementation challenges included difficulties tracking referred patients, stock-outs of key supplies, difficulties with machine maintenance, and prohibitive user fees. Providers were trained to independently monitor services, identify gaps, and take corrective actions. Following dissemination of the results that demonstrated the acceptability and feasibility of the CECAP program, the Burkina Faso Ministry of Health included CECAP services in its minimum service delivery package in 2016. Essential components for such programs include provider training on VIA, cryotherapy, and LEEP; provider and patient demand generation; local equipment maintenance; consistent supply stocks; referral system for LEEP; non-prohibitive fees; and a monitoring data collection system.

Breast Cancer Prevention: Current Approaches and Future Directions.

The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease. Current strategies to decrease a woman's risk of developing breast cancer include primary prevention, such as avoiding tobacco, exogenous hormone use and excess exposure to ionizing radiation, maintaining a normal weight, exercise, breastfeeding, eating a healthy diet and minimizing alcohol intake. Chemoprevention medications are available for those at high risk, though they are underutilized in eligible women. Mastectomy and/or bilateral oophorectomy are reasonable strategies for women who have deleterious mutations in genes that dramatically increase the risk of developing cancer in either breast. There are a variety of strategies in development for the prevention of breast cancer. Personalized approaches to prevent breast cancer that are being developed focus on advances in precision medicine, knowledge of the immune system and the tumor microenvironment and their role in cancer development. Advances in our understanding of how breast cancer develops are allowing investigators to specifically target populations who are most likely to benefit. Additionally, prevention clinical trials are starting to evaluate multi-agent cancer prevention approaches, with the hope of improved efficacy over single agents. Finally, there is a push to increase the use of chemopreventive agents with proven efficacy, such as tamoxifen and raloxifene, in the prevention of breast cancer.

Epidemiology and cost of cervical cancer care and prevention in Apulia (Italy), 2007/2016.

According to recent estimates, cervical cancer is worldwide the second most common cancer in females and the fourth overall. The number of deaths for cervical cancer is around 7.5% of all female cancer deaths. Cervical cancer is the only tumour with a known necessary cause, the HPV infection and, globally, HPV is the most common sexually transmitted infection. Two major approaches for cervical cancer prevention have been designed: primary prevention by HPV vaccination and secondary prevention by screening. The aim of our study is to design an overview of epidemiology, cost of the therapies and cost of prevention measures (screening and vaccines) 9 years after the introduction of anti-HPV vaccination in the Apulia Regional Immunization Program. Retrospective observational study. To describe the epidemiology of cervical cancer, we analysed data from the Apulia regional archive of hospital discharge forms (SDO). We considered all records referred to cervical cancer using the ICD 9 code 180.xxx both in primary and secondary diagnosis, for the years 2007-2016. Subjects living in Apulia have been considered. Costs of hospitalization were computed considering generated Diagnosis Related Groups (DRG). To describe the Apulian screening program, we analysed data from Regional Screening Data warehouse; the cost of the single test was established according to the Tariff List from the Ministry of Health. Finally, vaccination data were extracted by Regional Immunization Database and official ex-factory price has been used to calculate the costs of immunization program. From 2007 to 2016, an important decrease in the incidence rate of cervical cancer in Apulia has been noted, ranging from 43.7 per 100,000 residents in 2007 to 21.0 per 100,000 residents in 2016. From an economic point of view, a clear reduction (39%) is observed in hospitalization costs over time. Total costs of prevention programs increased over time and globally exceed € 54,000,000, with a decreasing trend for vaccine prophylaxis and an increasing trend for screening. The incidence and costs of cervical cancer in Apulia, although already significantly decreasing, likely will be further reduced since 2027-2032, when we can observe the effects of vaccine prophylaxis on the burden of disease; on this occasion it will be also possible to quantify the actual cost-effectiveness of the vaccine. In our opinion, in the future the Apulia healthcare executives should enhance and improve the active screening test offer, without underestimating the importance of sexual education in young people, especially in those who have not had sexual debut yet.

Insights on Cancer Preventive Approaches Using Plant Based Extracts

Cancer is one of the fatal diseases, and it continues to pose a significant health problem worldwide. Although great efforts are being done to discover a cure, cancer still remains a very prominent cause of mortality in humans, and its effective treatment is a formidable challenge. Although cancer therapies have been performed throughout the history, the efficacy of the treatment still remains a challenge. In recent years, natural product compounds have become the first choice of treatment in many cases. Gene therapy, in addition, is offering selective new methods for treatment. This review emphasizes the advancements cancer treatment using naturally derived products with significantly less toxicity and more efficacies; thereby enhancing the understanding of different cancers and potential of the plant based extract in the anti-cancer field.

Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

Eradicating gastric cancer.

Gastric cancer develops in a stepwise manner along the inflammation–metaplasia–dysplasia–carcinoma pathway. Similar to several infection‐associated cancers, such as liver cancer (associated with viral hepatitis B and C) and cervical cancer (associated with human papilloma virus), Helicobacter pylori infection is the main trigger of this carcinogenic cascade. Observational studies with baseline serological testing and more than 10 years of follow up have found that chronic H. pylori infection is related to about 90% of gastric cancers and thus removal of this bacterium from a population has been postulated to eradicate the occurrence of gastric cancer.1 This hypothesis has stimulated numerous investigations indicating not only the magnitude of benefit obtained from a short‐course antibiotic treatment but also the principles to help policymakers design preventive services that maximize the effectiveness of using this strategy. The application of this antibiotic‐based approach for gastric cancer prevention has been hindered by a lack of answers to four important questions (Table ​(Table1).1). There are now satisfactory answers to these questions. Table 1 Questions about the elimination of gastric cancer through H. pylori eradication.

The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice

Epidemiologic studies report improved breast cancer survival in women who receive ketorolac (Toradol) for postoperative pain relief compared with other analgesic agents. Ketorolac is a racemic drug. The S-enantiomer inhibits cyclooxygenases; R-ketorolac is a selective inhibitor of the small GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), which are signaling molecules up-regulated during breast cancer progression and metastasis. The goal of this study was to determine whether R-ketorolac altered breast cancer development in the mouse mammary tumor virus-polyoma middle T-antigen model. Mice were administered ketorolac orally at 1 mg/kg twice daily to approximate the typical human dose. Mammary glands were analyzed for tumor number and immunohistochemical markers of proliferation and differentiation. R-ketorolac treatment significantly reduced mammary epithelial proliferation, based on Ki67 staining, and suppressed tumor development. Proliferative mammary epithelium from R-ketorolac-treated mice displayed greater differentiation, based on significantly higher total E-cadherin and decreased keratin 5 staining than epithelium of placebo-treated mice. No differences were detected inestrogen receptor, progesterone receptor, β-catenin, or vimentin expression between placebo and R-ketorolac treatment groups. These findings indicate that R-ketorolac treatment slows tumor progression in an aggressive model of breast cancer. R-ketorolac may thus represent a novel therapeutic approach for breast cancer prevention or treatment based on its pharmacologic activity as a Rac1 and Cdc42 inhibitor.