JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac019. doi: 10.1093/jncics/pkac019.

ABSTRACT

BACKGROUND: Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed.

METHODS: We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided.

RESULTS: Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; Ptrend = .05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; Ptrend = .03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; Ptrend = .02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; Ptrend < .001 for overall and lung cancer, respectively).

CONCLUSIONS: Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.

PMID:35603848 | DOI:10.1093/jncics/pkac019

JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac017. doi: 10.1093/jncics/pkac017.

ABSTRACT

Rural populations continue to experience persistent cancer disparities compared with urban populations particularly in cancers that can be prevented or detected early through screening and vaccination. Although the National Cancer Institute and the larger cancer research community have identified rural community partnerships as the foundation for reducing the disparities, we have identified limited application of community-based participatory research in cancer prevention and control research. Guided by the Community-Based Participatory Research Conceptual Model and our collective experience, we provide a framework for a community-cancer center partnership that focuses on promoting health equity. In this commentary, we articulate that the partnership process must foster capacity for communities and cancer centers, strive for rural representation in clinical trials and biobanking, build a pipeline for dissemination and implementation research, and create a bidirectional flow of knowledge between communities and academic institutions. Authentic partnerships with rural communities should be the ultimate goal of cancer centers, and the process described in this commentary can serve as an initial platform to build capacity and continue to strive toward that goal.

PMID:35603844 | DOI:10.1093/jncics/pkac017

JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac009. doi: 10.1093/jncics/pkac009.

ABSTRACT

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients.

METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history.

RESULTS: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality.

CONCLUSIONS: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.

PMID:35603841 | DOI:10.1093/jncics/pkac009

Front Cell Infect Microbiol. 2022 May 4;12:899248. doi: 10.3389/fcimb.2022.899248. eCollection 2022.

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer and eradication of H. pylori is recommended as an effective gastric cancer prevention strategy. The infected individuals show microbial dysbiosis of gastric microbiota. In recent years, agrowing number of studies have focused on gastric microbiota changes following H. pylori eradication. In the present study, we aim to evaluate the influence of successful H. pylori eradication on the short-term and long-term alterations of human gastric microbiota using a method of systematic review and meta-analysis.

METHODS: We did a systematic search based on three databases (PubMed, EMBASE, and Web of Science) in November 2021. Additional articles were also identified by reviewing references cited in the included papers. Human studies that reported changes in gastric microbiota following successful H. pylori eradication were enrolled. PROSPERO registration number: CRD42021293796.

RESULTS: In total, nine studies enrolling 546 participants were included. Regarding quadruple therapy, alpha diversity indexes increased within 1 month after eradication; significant differences in gastric microbial community structure between before and after eradication were also seen within 1 month. The trends of the above-mentioned diversity changes persisted with a follow-up of 6 months. The microbial composition altered significantly after eradication and the relative abundance of H. pylori-related taxa decreased. Accordingly, gastric commonly dominant commensals were enriched. Bioinformatic analyses of microbiota functions showed that bacteria reproduction-related pathways were down-regulated and pathways of gastric acid secretion, etc. were up-regulated. For triple therapy, similar trends of alpha diversity and beta diversity changes were observed in the short-term and long-term follow-up. Also, after eradication, H. pylori was not the gastric dominant bacteria and similar changes in gastric microbial composition were found. For gastric microbial interactions, a decrease in microbial interactions was seen after eradication. Additionally, regarding whether successful H. pylori eradication could restore gastric microbiota to uninfected status, the results remain controversial.

CONCLUSION: In conclusion, successful H. pylori eradication could reverse the gastric microbiota dysbiosis and show beneficial effects on gastric microbiota. Our findings may provide new insight for exploring the role of H. pylori and the whole gastric microbiota in gastric carcinogenesis.

PMID:35601105 | PMC:PMC9114356 | DOI:10.3389/fcimb.2022.899248

Med Oncol. 2022 May 23;39(5):98. doi: 10.1007/s12032-022-01688-x.

ABSTRACT

Anaplastic thyroid cancer cases with poor prognosis are associated with epigenetic modifications such as abnormal DNA methylation. Epigallocathesin-3-gallate (EGCG) is a polyphenol compound of green tea that is still under investigation on its role in cancer prevention. EGCG is known as an epigenetic diet in DNA methyltransferase inhibitor. The cytotoxic effects of Dabrafenib, EGCG, and dabrafenib in combination with EGCG were assessed by using WST-8 assay; and also, Flow cytometry was utilized to identify cells undergoing apoptosis after treatments of the SW-1736 cells. We investigated the mRNA expression of genes involved in epigenetic events in SW-1736 cells by real-time qRT-PCR following the treatments. We demonstrated for the first time that the Dabrafenib-EGCG combination reduced cell viability significantly depending on concentration and induced apoptosis by 8.49-fold through investigating the additive effect together on SW-1736 cells. The IC₅₀ doses of Dabrafenib and EGCG for 48 h were determined as 6.7 μM and 22.5 μM, respectively. The results of qRT-PCR demonstrated that the Dabrafenib-EGCG combination significantly caused the down-regulation of genes involved in epigenetic regulation. We suggest that the combination of Dabrafenib and EGCG following in vivo phase studies will contribute as an alternative treatment option for the treatment of ATC.

PMID:35599263 | DOI:10.1007/s12032-022-01688-x

Gastroenterol Clin North Am. 2022 Jun;51(2):441-455. doi: 10.1016/j.gtc.2021.12.015. Epub 2022 Apr 27.

ABSTRACT

Health care maintenance is critical for patients with inflammatory bowel disease (IBD), particularly for those receiving immunosuppressive medications. Vaccination recommendations for potentially preventable diseases, cancer prevention recommendations, and assessment of bone health and mood disorders are discussed in this article. Staying up to date with health care maintenance is of utmost importance, and all gastroenterologists caring for patients with IBD should be able to make recommendations regarding preventative care of these patients.

PMID:35595424 | DOI:10.1016/j.gtc.2021.12.015

Cancer J. 2022 May-Jun 01;28(3):224-240. doi: 10.1097/PPO.0000000000000596.

ABSTRACT

PURPOSE: Current concepts regarding estrogen and its mechanistic effects on breast cancer in women are evolving. This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model.

METHODS: This article reviews previously published studies from the authors and articles pertinent to the data presented.

RESULTS: We discuss the concepts of adaptive hypersensitivity that develops in response to long-term deprivation of estrogen and results in both increased cell proliferation and apoptosis. The effects of menopausal hormonal therapy on breast cancer in postmenopausal women are interpreted based on the tumor kinetic model. Studies of the administration of a tissue selective estrogen complex in vitro, in vivo, and in patients are described. We review the various clinical studies of breast cancer prevention with selective estrogen receptor modulators and aromatase inhibitors. Finally, the effects of the underlying risk of breast cancer on the effects of menopausal hormone therapy are outlined.

DISCUSSION: The overall intent of this review is to present data supporting recent concepts, discuss pertinent literature, and critically examine areas of controversy.

PMID:35594470 | DOI:10.1097/PPO.0000000000000596

Front Immunol. 2022 May 3;13:888250. doi: 10.3389/fimmu.2022.888250. eCollection 2022.

ABSTRACT

Tumor protein 53 (TP53) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro, resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.

PMID:35592333 | PMC:PMC9112561 | DOI:10.3389/fimmu.2022.888250

Med (N Y). 2021 Aug 13;2(8):903-907. doi: 10.1016/j.medj.2021.07.004.

ABSTRACT

Transgender, non-binary, and gender non-conforming people, also referred to as gender minorities, have unique cancer prevention, treatment, and care needs and experience cancer health disparities compared to the cisgender population. We present four composite cases of the cancer care challenges experienced by gender minorities.

PMID:35590166 | DOI:10.1016/j.medj.2021.07.004

Med (N Y). 2022 Jan 14;3(1):3-5. doi: 10.1016/j.medj.2021.12.007.

ABSTRACT

HPV vaccination has been routinely recommended in the US since 2006. A new article from Falcaro et al.¹ adds to the growing body of evidence to demonstrate HPV vaccination prevents cancer. These results are timely and important as public health professionals globally seek to mitigate the effects of vaccination hesitancy and build confidence in vaccinations.

PMID:35590142 | DOI:10.1016/j.medj.2021.12.007

BMJ Open. 2022 May 19;12(5):e059754. doi: 10.1136/bmjopen-2021-059754.

ABSTRACT

OBJECTIVES: Quantitative faecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening in the Western countries, whereas qualitative FITs are preferred in China. The present study aimed to compare the screening yield between one-sample quantitative FIT and two-sample qualitative FIT for CRC screening.

DESIGN: A cross-sectional study.

SETTING: A population-based CRC screening programme was conducted in 28 communities in Haining City, Zhejiang Province, China.

PARTICIPANTS: Consecutive participants aged 40-74 years were invited to undergo the CRC screening programme. Two-sample qualitative FITs were offered between January 2019 and December 2019, and one-sample quantitative FIT was offered between August 2019 and February 2020.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were detection rates of advanced neoplasms, including CRCs and advanced adenomas. Secondary outcomes were positivity rates and colonoscopy resource demand for the two FITs. The positivity thresholds were 20 µg and 1-5 µg haemoglobin per gram of faeces for the quantitative and qualitative FITs, respectively.

RESULTS: A total of 19 131 and 28 804 invitees were assigned to the two-sample qualitative and one-sample quantitative groups, respectively. Positivity rates were 14.2% for the two-sample qualitative FIT and 5.4% for the one-sample quantitative FIT. Detection rates of advanced colorectal neoplasms at colonoscopy using one-sample quantitative FIT and two-sample qualitative FIT were 17.6% (95% CI: 14.6% to 20.6%) and 10.5% (95% CI: 8.7% to 12.4%), respectively. Both detection rates of cancer and advanced adenoma were higher in the one-sample quantitative FIT group than those in the two-sample qualitative FIT group. Moreover, one-sample quantitative FIT significantly reduced the colonoscopy load for detection of one advanced neoplasm case (5, 95% CI: 5 to 7) than the two-sample qualitative FIT (10, 95% CI: 8 to 11).

CONCLUSIONS: The one-sample quantitative FIT for CRC screening increases the detection rate of advanced neoplasia and reduces the colonoscopy workload compared with the two-sample qualitative FIT.

PMID:35589365 | DOI:10.1136/bmjopen-2021-059754

PLoS One. 2022 May 19;17(5):e0267189. doi: 10.1371/journal.pone.0267189. eCollection 2022.

ABSTRACT

BACKGROUND: Cancer is the leading cause of morbidity and mortality globally. In Ethiopia, 5.8% of deaths are attributed to cancer. Therefore, this study aimed to examine the cancers preventive practice and associated factors in North West Ethiopia, 2019.

METHODS: A community-based cross-sectional study was conducted among Bahir Dar city residents. A multistage sampling technique was used to select 845 study participants. Data were collected through a validated interviewer administered questionnaire. The questionnaire was adapted from the American cancer association cancer prevention toolkit. Descriptive statistics were computed and presented in charts and texts. The model fitness was checked using Hosmer and Lemeshow goodness of fit (P > 0.05). Bivariable and multivariable logistic regressions were used to identify factors associated with cancer preventive practice. A p-value < 0.2 at bivariate analysis was candidate variables for multivariable logistic regression analysis. Finally, p-value of < 0.05 was considered as a statistically significant predictor for cancer preventive practice at the 95% confidence interval.

RESULT: A total of 845 study participants took part in the study. Nearly 63% of the respondents were females. About 28% (95%CI: 24, 30) of the study participants had good preventive practice. Age ≥ 45 years (AOR = 0.31; 95%CI: 0.15, 0.62), female (AOR = 0.50, 95%CI: 0.35, 0.71) family member with cancer (AOR = 1.68, 95%CI: 1.07, 2.62) and had good knowledge (AOR = 1.66, 95%CI: 1.14, 2.42) were the identified determinants of cancer preventive practices.

CONCLUSION: This study revealed that the level of cancer preventive practices was low. Family member with cancer, knowledge about cancer, older age, and being female were significantly associated with cancer preventive practices. This finding underscores the importance of interventions to enhance cancer preventive practices.

PMID:35587937 | PMC:PMC9119519 | DOI:10.1371/journal.pone.0267189

JAMA Netw Open. 2022 May 2;5(5):e2212246. doi: 10.1001/jamanetworkopen.2022.12246.

ABSTRACT

IMPORTANCE: Considering reported rural-urban cancer incidence and mortality trends, rural-urban cancer survival trends are important for providing a comprehensive description of cancer burden. Furthermore, little is known about rural-urban differences in survival trends by racial and ethnic groups.

OBJECTIVE: To examine national rural-urban trends in 5-year cancer-specific survival probabilities for lung, prostate, breast, and colorectal cancers in a diverse sample of racial and ethnic groups.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used an epidemiologic assessment with 1975 to 2016 Surveillance, Epidemiology, and End Results (SEER) data to analyze patients diagnosed no later than 2011. Patients were classified as living in rural and urban counties based on the 2013 Rural-Urban Continuum Codes.

MAIN OUTCOMES AND MEASURES: The 5-year cancer-specific survival probability of urban and rural patients for each cancer type was estimated by fitting Cox proportional hazard regression models accounting for race, ethnicity, tumor characteristics, and other sociodemographic characteristics. A generalized linear regression model was used to estimate the mean estimated probability of survival for each stratum. Joinpoint regression analysis estimated periods of significant change in survival.

RESULTS: In this study, data from 3 659 417 patients with cancer (median [IQR] age, 67 [58-76]; 1 918 609 [52.4%] male; 237 815 [6.5%] Hispanic patients; 396 790 [10.8%] Black patients; 2 825 037 [77.2%] White patients) were analyzed, including 888 338 patients with lung cancer (24.3%), 750 704 patients with colorectal cancer (20.5%), 987 826 patients with breast cancer (27.0%) breast, and 1 023 549 patients with prostate cancer (28.0%). There were 430 353 rural patients (11.8%). Overall, there was an equal representation of rural and urban men. Rural patients were likely to be non-Hispanic White individuals, have more cases of distant tumors, and be older. Rural and non-Hispanic Black patients for all cancer types often had shorter survival. From 1975 to 2016, the 5-year lung cancer survival rate was shorter for non-Hispanic Black rural patients in 1975 at 48%, while increasing to 57% for both non-Hispanic Black urban and rural patients in 2011, but still the shortest among all cancer types. In 1975, the longest survival rate was observed in urban Asian and Pacific Islander patients with breast cancer at 86%, and in 2011, the longest survival rate was observed in urban non-Hispanic White patients with XX cancer at 92%.

CONCLUSIONS AND RELEVANCE: Even after accounting for sociodemographic and tumor characteristics, these findings suggest that non-Hispanic Black patients with cancer are particularly vulnerable to cancer burden, and resources are urgently needed to reverse decades-old survival trends.

PMID:35587350 | DOI:10.1001/jamanetworkopen.2022.12246

Bioengineered. 2022 May;13(5):12435-12445. doi: 10.1080/21655979.2022.2075300.

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignant tumors. Tumor-associated macrophages (TAMs) promote the progression of CRC, but the mechanism is not completely clear. The present study aimed to reveal the expression and function of FAM198B in TAMs, and the role of FAM198B in mediating macrophage polarization in CRC. The role of FAM198B in macrophage activity, cell cycle, and angiogenesis was evaluated by CCK-8 assay, flow cytometry, and vasculogenic mimicry assay. The effects of FAM198B on macrophage polarization were determined by flow cytometry. The function of FAM198B-mediated macrophage polarization on CRC progression was evaluated by transwell assays. Bioinformatic analyses and rescue assays were performed to identify biological functions and signaling pathways involved in FAM198B regulation of macrophage polarization. Increased FAM198B expression in TAMs is negatively associated with poor CRC prognosis. Functional assays showed that FAM198B promotes M2 macrophage polarization, which leads to CRC cell proliferation, migration, and invasion. Mechanistically, FAM198B regulates the M2 polarization of macrophages by targeting SMAD2, identifying the SMAD2 pathway as a mechanism by which FAM198B promotes CRC progression through regulating macrophage polarization. These findings provide a possible molecular mechanism for FAM198B in TAMs in CRC and suggest that FAM198B may be a novel therapeutic target in CRC.

PMID:35587159 | DOI:10.1080/21655979.2022.2075300

Front Public Health. 2022 May 2;10:878703. doi: 10.3389/fpubh.2022.878703. eCollection 2022.

ABSTRACT

INTRODUCTION: The first line of action against cancer is primary and secondary prevention. Increased efforts are needed in countries where cancer mortality is high and the healthcare system is inefficient. Objectives: Our aim was to present a new solution to identify and fill gaps in health education services in accordance with the European Code Against Cancer (ECAC).

MATERIALS AND METHODS: This study was carried out in a rural population of 122 beneficiaries of health education workshops financed by the Polish Cancer League. A self-developed questionnaire was used. PQStat v1.6.8. was also applied.

RESULTS: Our respondents were mostly farmers (53.3%) and manual workers (16.4%). Most participants self-assessed their health knowledge as good (46.7%). While 42% of all respondents claimed to know the healthy eating pyramid, only 8.2% correctly recognised all of its principles and 23.8% realised the importance of limiting the consumption of red meat. The most commonly recognised cancer risk factor were genetics (72.1%), stimulants such as alcohol or tobacco (51.5%) and environmental pollution (45.1%). UV radiation was not commonly recognised as a risk factor by respondents despite high occupational exposure in this population. We found a high percentage of male smokers. As many as 64.8% of respondents had not been counselled on cancer prevention in their clinics. A family history of cancer (FHC) did not differentiate respondents' health knowledge, health behaviors, or frequency of receiving cancer prevention counselling. Health education and health promotion in the region were unsatisfactory.

CONCLUSIONS: Primary health care (PHC) should become more involved in promoting cancer prevention knowledge. One way could be to encourage health professionals to promote the ECAC. Cancer prevention should target especially persons with FHC and focus on modifiable cancer risk factors. At the workshops we were able to adjust the strength of each ECAC recommendation to best fit the target audience. By diagnosing and targeting specific communities, we can draw the attention of PHC staff and decision-makers to local health promotion needs, which is a good starting point for improving the situation. However, larger scale projects are needed to help design specific solutions to support primary healthcare in promoting ECAC.

PMID:35586014 | PMC:PMC9109786 | DOI:10.3389/fpubh.2022.878703

Sci Rep. 2022 May 18;12(1):8316. doi: 10.1038/s41598-022-11904-3.

ABSTRACT

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, ¹HNMR, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC₅₀ (200-1.75 µM). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC₅₀ = 2.3 µM) than cisplatin (IC₅₀ = 107 µM) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth.

PMID:35585092 | PMC:PMC9117324 | DOI:10.1038/s41598-022-11904-3

Cell Rep Med. 2022 May 17;3(5):100642. doi: 10.1016/j.xcrm.2022.100642.

ABSTRACT

Derosa et al.¹ demonstrated that intestinal Akkermansia muciniphila predicts vigorous response to immunotherapy in non-small-cell lung cancer. Baseline level of this microbe has better value than PD-L1 expression and represents a unique approach for stratifying patients that can benefit from immunotherapy.

PMID:35584634 | DOI:10.1016/j.xcrm.2022.100642

JNCI Cancer Spectr. 2022 May 2;6(3):pkac027. doi: 10.1093/jncics/pkac027.

ABSTRACT

BACKGROUND: Human studies investigating the prospective relationship between microbial metabolites and colorectal cancer (CRC) risk are lacking. We tested whether higher serum bile acids (BAs) and lower short-chain fatty acids (SCFAs) were associated with CRC risk.

METHODS: In baseline serum collected more than 30 years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n = 262 cases; women: n = 233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n = 598 cases). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for BA and SCFA quartiles and summary measures with CRC overall and by anatomic location using multivariable conditional logistic regression models. PLCO analyses were stratified by sex. All statistical tests were 2-sided.

RESULTS: In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1 = 2.85, 95% CI = 1.45 to 5.60, Qtrend = 0.011), glycodeoxycholic (OR Q4 v Q1 = 3.45, 95% CI = 1.79 to 6.64, Qtrend = 0.006), taurodeoxycholic (OR Q4 v Q1 = 2.36, 95% CI = 1.22 to 4.55, Qtrend = 0.023), and glycolithocholic acid (ORQ4 v Q1 = 2.71, 95% CI = 1.41 to 5.22, Qtrend = 0.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR = 0.55, 95% CI = 0.31 to 0.98, Ptrend = .03). Associations for total BAs and SCFAs were strongest among women with proximal colon cancer. No statistically significant associations were observed for BA or SCFA measures among men.

CONCLUSIONS: Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.

PMID:35583137 | PMC:PMC9115675 | DOI:10.1093/jncics/pkac027

BMC Med Inform Decis Mak. 2022 May 17;22(1):135. doi: 10.1186/s12911-022-01874-x.

ABSTRACT

To improve cancer care in Indiana, a telementoring program using the Extension for Community Healthcare Outcomes (ECHO) model was introduced in September 2019 to promote best-practice cancer prevention, screening, and survivorship care by primary care providers (PCPs). The aim of this study was to evaluate the program's educational outcomes in its pilot year, using Moore's Evaluation Framework for Continuing Medical Education and focusing on the program's impact on participants' knowledge, confidence, and professional practice. We collected data in 22 semi-structured interviews (13 PCPs and 9 non-PCPs) and 30 anonymous one-time surveys (14 PCPs and 16 non-PCPs) from the program participants (hub and spoke site members), as well as from members of the target audience who did not participate. In the first year, average attendance at each session was 2.5 PCPs and 12 non-PCP professionals. In spite of a relatively low PCP participation, the program received very positive satisfaction scores, and participants reported improvements in knowledge, confidence, and practice. Both program participants and target audience respondents particularly valued three features of the program: its conversational format, the real-life experiences gained, and the support received from a professional interdisciplinary community. PCPs reported preferring case discussions over didactics. Our results suggest that the Cancer ECHO program has benefits over other PCP-targetted cancer control interventions and could be an effective educational means of improving cancer control capacity among PCPs and others. Further study is warranted to explain the discrepancies among study participants' perceptions of the program's strengths and the relatively low PCP participation before undertaking a full-scale effectiveness study.

PMID:35581580 | PMC:PMC9112252 | DOI:10.1186/s12911-022-01874-x

J Interferon Cytokine Res. 2022 May;42(5):220-234. doi: 10.1089/jir.2021.0214.

ABSTRACT

Immune-associated biomarkers can predict lung metastases from colorectal cancer. Differentially expressed genes (DEGs) were screened from sample data extracted from gene expression omnibus (GEO) database. The DEGs were screened from the lung metastasis (LM) and primary cancer (PC) groups of the Moffitt Cancer Center cohort dataset. Then, the tumor immune microenvironment and abundance of immune cell infiltration analyses were performed, and the immune-related DEGs were retrieved. In addition, the transcription factor (TF)-miRNA-mRNA network was constructed and enrichment analyses of the immune-related DEGs and upregulated and downregulated DEGs were carried out. Then, the protein-protein interaction (PPI) network was conducted and the drug-gene interaction was predicted. A total of 268 DEGs were screened. The Immune_Score of samples in the LM group was significantly higher compared with the PC group. The infiltration ratio of M0 macrophages and M2 macrophages of samples was higher than others. A total of 54 immune-related DEGs in M0 macrophages were screened. Moreover, the TF-miRNA-mRNA network was constructed among 8 miRNA-mRNA and 50 TF-mRNA, and the secreted phosphoprotein 1 was regulated by 12 TFs, and the oxidized low-density lipoprotein receptor 1 was regulated by 3 miRNAs and 3 TFs. The TF SAM pointed domain containing ETS TF was also a downregulated DEG. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEGs in the TF-miRNA-mRNA network were mainly involved in the interleukin-7 signaling pathway and cell adhesion molecules. In total, 23 protein interactions in this PPI network of M0 macrophage cells were involved in 27 mRNAs. There were 38 drug-gene interactions of immune-related DEGs of M0 macrophage cells predicted to contain 34 small molecule drugs and 8 mRNAs. Finally, the CON cohort dataset verified that the infiltration ratio of M0 and M2 macrophages of the samples was higher.

PMID:35576491 | DOI:10.1089/jir.2021.0214

J Immunol Res. 2022 May 6;2022:3351268. doi: 10.1155/2022/3351268. eCollection 2022.

ABSTRACT

BACKGROUND: Various natural compounds are effective in cancer prevention and treatment with fewer side effects than conventional radiotherapy and chemotherapy. Considering the uncertainty of the antitumor mechanism of Echinacoside (Ech) and the fact that no study on Ech against non-small cell lung cancer (NSCLC) has been explored previously, this study inquired into the anti-NSCLC effect of Ech and explored its potential mechanisms.

METHODS: The IC₅₀ to Ech of the NSCLC cells was calculated based on a series of cell viability assays. Different concentrations of Ech were used to treat the cells; the proliferation activity of the cells was evaluated using EdU staining. Mitochondrial membrane potential was detected by JC-1 staining. Levels of cytokines IL-1β and IL-18 were measured by ELISA. GSH and MDA levels were measured by microplate reader. Expression of cytochrome c, NLRP3, caspase-1, IL-1β, c-Myc, c-Fos, and Raf/MEK/ERK pathway proteins was evaluated by western blot. Meanwhile, we used xenograft, immunohistochemical staining, and H&E staining to evaluate the pharmacological effects of Ech in mice in vivo.

RESULTS: ECH inhibited the proliferation of NSCLC cells. Ech increased the expression of pyroptosis-related proteins. Besides, Ech perturbed the mitochondrial membrane potential with the release of mitochondrial cytochrome c, accompanied by increased oxidative stress. Ech inhibited the phosphorylation levels of Raf/MEK/ERK signaling pathway and subsequently reduced c-myc and c-fos protein expression. In addition, Ech effectively restrained the growth of tumors in vivo.

CONCLUSIONS: Ech inhibited the Raf/MEK/ERK signaling. Impaired mitochondria activated inflammasome, which in turn led to the pyroptosis of NSCLC cells. These findings can provide some ideas on how to use pyroptosis to treat NSCLC.

PMID:35571569 | PMC:PMC9106467 | DOI:10.1155/2022/3351268

Front Public Health. 2022 Apr 29;10:845400. doi: 10.3389/fpubh.2022.845400. eCollection 2022.

ABSTRACT

The COVID-19 pandemic has dramatically impacted higher education institutions in the United States (US). Given the dangers of close social interaction in spreading COVID-19, colleges and universities closed their campuses to minimize and often restrict face-to-face instruction of any kind, including supplemental skill development training and experiential learning. In exchange, higher education institutions implemented online learning strategies to continue education for students, including in-person experiential field experiences. This paper describes the adaptation of an in-person experiential field experience into an eight-day virtual workshop as a result of COVID-19 restrictions along with results from participant surveys evaluating pre-and post-test changes in knowledge and their overall assessment of the virtual workshop. This workshop, the Public Health and Cancer Research Workshop (PHCRW), was tailored for students from health-related graduate programs with the primary goal of introducing students to the causes and impacts of cancer disparities in the US/Mexico border region and research related to mitigating those disparities. The course facilitators added a professional development curriculum necessary for student success and the pursuit of advanced degrees such as academic/job interviewing skills and scientific and grant writing. The objectives were for students to (1) understand introductory and intermediate curriculum on public health, cancer, and cancer research; (2) examine the interrelationships among factors impacting public health problems; (3) describe the components of the research process; (4) describe various components of scientific writing; and (5) demonstrate professional strategies associated with school admission and employment. Students completed pre-and post- self-assessments that indicated gains in knowledge about cancer topics, particularly cancer prevention strategies (M _pre = 3.43; M _post = 4.43), social determinants associated with cancer (M _pre = 3.29; M _post = 4.43), and cancer rates by characteristics (M _pre = 3.43; M _post = 4.43). Additionally, students overwhelmingly stated that they appreciated the opportunity to supplement their educational experience in a virtual format. Though the virtual format proved challenging in some respects, students expressed high satisfaction with the workshop. In addition to achieving the goals, the workshop successfully increased students' skills, knowledge, and self-confidence. Despite the last-minute adaptation of the PHCRW, students' satisfaction indicated that this program was an overall success.

PMID:35570916 | PMC:PMC9099227 | DOI:10.3389/fpubh.2022.845400

BMC Womens Health. 2022 May 14;22(1):169. doi: 10.1186/s12905-022-01728-8.

ABSTRACT

BACKGROUND: Little research has been conducted to explore variables associated with the healthcare providers' (HCPs) understanding and recommendation of human papillomavirus vaccine (HPV) since the vaccine was approved for use in China.

METHODS: A large-scale cross-sectional survey was conducted in southern China covering Guangdong, Guangxi, and Hainan provinces between April 2019 and October 2019. Firstly, descriptive analysis was used to access awareness, knowledge, barriers, and recommendations toward HPV vaccine among all participants. Multi-variable logistic regression was further applied to explore potential factors associated with awareness, acknowledgment of HPV vaccine, and recommendation behaviors toward HPV vaccine.

RESULTS: 2075 questionnaires were collected, and 2054 were included in the final analysis. In total, 77.9% of participants have heard of HPV vaccine and obtained sub-optimal HPV/HPV vaccine knowledge scores with a mean (SD) of 13.8 (3.5) out of a maximum score of 23. 68.1% HCPs reported that they have recommended HPV vaccine to others. Province and profession were the most significant characteristics associated with awareness, knowledge score, and recommendation behavior toward HPV vaccine. HCPs in Guangdong obtained a much better knowledge score [Mean (SD) = 15.5 (3.0)] and reported higher recommendation behavior (82.8%). Compare with HCPs from the Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC), and obstetrician-gynecologists, other non-HPV closely related professions showed a less competent knowledge of HPV and HPV vaccine [Mean (SD) = 12.5 (3.0)] and lower frequency of recommendation behavior on vaccination (58.1%). The difference in HPV vaccine knowledge among different professions was concentrating on the items about clinical pathology of HPV and the practical aspects of HPV vaccine. Educational level and title were also closely associated with their knowledge of HPV and its vaccine. Besides, knowledge scores independently determined with recommendation behavior (OR = 1.18, 95% CI 1.13-1.23).

CONCLUSION: Knowledge level of HPV and HPV vaccine as well as recommendation behavior toward HPV vaccine were relatively lower in southern China and differed significantly between provinces. Profession-specific gaps on the knowledge level of HPV and HPV vaccine emphasized the need for targeted education and training to improve HCPs' engagement in the promotion of the HPV vaccine.

PMID:35568870 | PMC:PMC9107117 | DOI:10.1186/s12905-022-01728-8

Int J Environ Res Public Health. 2022 May 7;19(9):5694. doi: 10.3390/ijerph19095694.

ABSTRACT

Caribbean women experience a cervical cancer incidence rate that is three times higher than that among their North American counterparts. In this study, we performed a needs assessment of the knowledge and awareness of HPV, HPV vaccination, and cervical cancer and receipt of cervical cancer screening among an indigenous Caribbean community. We purposively recruited individuals aged ≥18 from a community health care clinic (n = 58) to complete a 57-item structured interview including items on demographics, cancer history, knowledge and awareness of HPV, HPV vaccines, cervical cancer, and cervical cancer screening. Participants' mean age was 47.1 years (SD: 14.4). Most were female (74.1%), were married/partnered (51.7%), had primary education (63.8%), and identified as Kalinago (72.4%). Whereas 79.5% had heard of cervical cancer, few had heard of HPV (19.6%) or the HPV vaccine (21.8%). Among those who knew someone with cancer, 90.9% had heard of the HPV vaccine, compared with only 9.1% of those who did not know anyone with cancer (p = 0.02). Access to HPV vaccination is an immediate, cost-effective cancer prevention priority for reducing the disproportionate burden of HPV-related cancers, particularly cervical cancer, in the Caribbean. We recommend culturally targeted education interventions to improve knowledge about HPV vaccination and the link between HPV and cervical cancer.

PMID:35565089 | PMC:PMC9105034 | DOI:10.3390/ijerph19095694

Int J Mol Sci. 2022 Apr 27;23(9):4800. doi: 10.3390/ijms23094800.

ABSTRACT

The growth modulating effects of the ovarian steroid hormones 17β-estradiol (E₂) and progesterone (PRG) on endocrine-responsive target tissues are well established. In hormone-receptor-positive breast cancer, E₂ functions as a potent growth promoter, while the function of PRG is less defined. In the hormone-receptor-positive Luminal A and Luminal B molecular subtypes of clinical breast cancer, conventional endocrine therapy predominantly targets estrogen receptor function and estrogen biosynthesis and/or growth factor receptors. These therapeutic options are associated with systemic toxicity, acquired tumor resistance, and the emergence of drug-resistant cancer stem cells, facilitating the progression of therapy-resistant disease. The limitations of targeted endocrine therapy emphasize the identification of nontoxic testable alternatives. In the human breast, carcinoma-derived hormone-receptor-positive MCF-7 model treatment with E₂ within the physiological concentration range of 1 nM to 20 nM induces progressive growth, upregulated cell cycle progression, and downregulated cellular apoptosis. In contrast, treatment with PRG at the equimolar concentration range exhibits dose-dependent growth inhibition, downregulated cell-cycle progression, and upregulated cellular apoptosis. Nontoxic nutritional herbs at their respective maximum cytostatic concentrations (IC₉₀) effectively increase the E₂ metabolite ratio in favor of the anti-proliferative metabolite. The long-term exposure to the selective estrogen-receptor modulator tamoxifen selects a drug-resistant phenotype, exhibiting increased expressions of stem cell markers. The present review discusses the published evidence relevant to hormone metabolism, growth modulation by hormone metabolites, drug-resistant stem cells, and growth-inhibitory efficacy of nutritional herbs. Collectively, this evidence provides proof of the concept for future research directions that are focused on novel therapeutic options for endocrine therapy-resistant breast cancer that may operate via E₂- and/or PRG-mediated growth regulation.

PMID:35563193 | PMC:PMC9105252 | DOI:10.3390/ijms23094800

Nat Commun. 2022 May 13;13(1):2665. doi: 10.1038/s41467-022-30392-7.

ABSTRACT

Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate pancreatic tumorigenesis; PanINs rarely progress to PDAC. Critical factors that promote this progression, especially targetable ones, remain poorly defined. We show that peroxisome proliferator-activated receptor-delta (PPARδ), a lipid nuclear receptor, is upregulated in PanINs in humans and mice. Furthermore, PPARδ ligand activation by a high-fat diet or GW501516 (a highly selective, synthetic PPARδ ligand) in mutant KRAS^G12D (KRAS^mu) pancreatic epithelial cells strongly accelerates PanIN progression to PDAC. This PPARδ activation induces KRAS^mu pancreatic epithelial cells to secrete CCL2, which recruits immunosuppressive macrophages and myeloid-derived suppressor cells into pancreas via the CCL2/CCR2 axis to orchestrate an immunosuppressive tumor microenvironment and subsequently drive PanIN progression to PDAC. Our data identify PPARδ signaling as a potential molecular target to prevent PDAC development in subjects harboring PanINs.

PMID:35562376 | PMC:PMC9106716 | DOI:10.1038/s41467-022-30392-7

Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2123261119. doi: 10.1073/pnas.2123261119. Epub 2022 May 13.

ABSTRACT

SignificanceThe mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is frequently elevated in human disease, including cancer, type 2 diabetes, metabolic disorders, and neurodegeneration. We identify SNAT7 as an important regulator of mTORC1. We believe this research will provide valuable insight about mTORC1 biology and may uncover novel therapeutic targets for patients.

PMID:35561222 | DOI:10.1073/pnas.2123261119

Endocrinology. 2022 Jun 1;163(6):bqac058. doi: 10.1210/endocr/bqac058.

ABSTRACT

The practice of oncology has dramatically changed in the last decade with the introduction of molecular tumor profiling into routine tumor diagnostics and the extraordinary progress in immunotherapies. However, there remains an unmet need to explore personalized dosing strategies that take into account the patient's sex and gender to optimize the balance between efficacy and toxicity for each individual patient. In this mini-review, we summarize the evidence on sex and gender differences in toxicity of anticancer therapies and present data on dose reduction and dose discontinuation rates for selected chemotherapies and targeted therapies. Finally, we propose the investigation of body composition (specifically fat-free muscle mass) as a viable approach for personalized treatment dosage.

PMID:35560216 | PMC:PMC9113364 | DOI:10.1210/endocr/bqac058

J Cancer Policy. 2021 Sep;29:100293. doi: 10.1016/j.jcpo.2021.100293. Epub 2021 Jul 12.

ABSTRACT

BACKGROUND: Alaska Native (AN) people have the highest rates of colorectal cancer (CRC) globally. Increasing CRC screening has been effective in reducing CRC-related morbidity and mortality in other populations.

OBJECTIVE: To examine recent descriptive epidemiology and longer-term CRC trends among AN people. To determine any changes in the descriptive epidemiology of CRC among AN people concurrent with increases in screening prevalence.

METHODS: We estimated age-specific CRC incidence and mortality rates 2000-2017. To examine longer-term trends in incidence and mortality 1990-2017, we conducted Joinpoint regression analyses of three-year rolling average incidence and mortality rates. We calculated descriptive statistics for two time-periods: 2000-2008, and 2009-2017. Finally, we examined five-year survival probability.

RESULTS: CRC incidence increased over time (1990-2017) among AN people aged less than 50 years, while there were modest declines in AN people older than 50 years old since 2000. Overall, AN CRC mortality rates declined between 1990 and 2004, but have been increasing steadily since that time. Comparing 2000-2008 with 2009-2017 we observed no difference in CRC incidence and mortality, age at diagnosis, tumor size, tumor location, or stage distribution. Survival analyses indicated no change in hazard of death between 2004-2008 and 2009-2017 (HR 1.02, 95 % CI: 0.74, 1.38, P = 0.93).

CONCLUSIONS: Colorectal cancer prevention and control efforts across the Alaska Tribal Health System have not yet resulted in reduced mortality rates, or induced earlier stage migration.

POLICY SUMMARY STATEMENT: Intensified efforts will be necessary to reduce the burden of CRC among this high-risk population. Continued and increased focus on primary and secondary prevention efforts is warranted.

PMID:35559952 | DOI:10.1016/j.jcpo.2021.100293

J Cancer Policy. 2021 Sep;29:100290. doi: 10.1016/j.jcpo.2021.100290. Epub 2021 May 29.

ABSTRACT

BACKGROUND: Brazil is a country of continental dimensions with great potential for the development of clinical studies across the whole territory to tackle the needs of the population. It is therefore important to obtain the national profile of clinical trials in order to identify local strengths and weaknesses in terms of productivity and study application. Thus, this paper aims to highlight the profiles of clinical studies on cancer developed and sponsored by hospitals, institutes, universities and international institutions in Brazil between 1997 and 2015.

METHODS: This is a retrospective and analytical study in which the content analysis method of Laurence Bardin was used. Data were collected from the clinicaltrials.govdatabase, where 783 clinical studies on cancer prevention, diagnosis and treatment were found; 188 (24 %) of these corresponded to national initiatives and 595 (76 %) to international initiatives.

RESULTS: The results show an increase in the number of national clinical studies, in particular phase III studies. There is a clear absence of national clinical studies focusing on the development of new chemical and biotechnological products in oncology.

CONCLUSION: The results indicate a regional imbalance in the distribution of national and international clinical trials.

POLICY SUMMARY: The present study aims to improve understanding of the profile of clinical studies registered in Brazil and to draw attention to the improvements needed in the health sector's productivity to address the national demand.

PMID:35559944 | DOI:10.1016/j.jcpo.2021.100290

Prev Chronic Dis. 2022 May 12;19:E25. doi: 10.5888/pcd19.210395.

ABSTRACT

Evidence-based interventions, including provider assessment and feedback, provider reminders, patient reminders, and reduction of structural barriers, improve colorectal cancer screening rates. Assessing primary care clinics' readiness to implement these interventions can help clinics use strengths, identify barriers, and plan for success. However, clinics may lack tools to assess readiness and use findings to plan for successful implementation. To address this need, we developed the Field Guide for Assessing Readiness to Implement Evidence-Based Cancer Screening Interventions (Field Guide) for the Centers for Disease Control and Prevention's (CDC's) Colorectal Cancer Control Program (CRCCP). We conducted a literature review of evidence and existing tools to measure implementation readiness, reviewed readiness tools from selected CRCCP award recipients (n = 35), and conducted semi-structured interviews with key informants (n = 8). We sought feedback from CDC staff and recipients to inform the final document. The Field Guide, which is publicly available online, outlines 4 assessment phases: 1) convene team members and determine assessment activities, 2) design and administer the readiness assessment, 3) evaluate assessment data, and 4) develop an implementation plan. Assessment activities and tools are included to facilitate completion of each phase. The Field Guide integrates implementation science and practical experience into a relevant tool to bolster clinic capacity for implementation, increase potential for intervention sustainability, and improve colorectal cancer screening rates, with a focus on patients served in safety net clinic settings. Although this tool was developed for use in primary care clinics for cancer screening, the Field Guide may have broader application for clinics and their partners for other chronic diseases.

PMID:35550244 | DOI:10.5888/pcd19.210395

BMC Cancer. 2022 May 11;22(1):527. doi: 10.1186/s12885-022-09578-1.

ABSTRACT

BACKGROUND: Cancer is the major cause of morbidity and mortality worldwide. The cancer burden varies within the regions of India posing great challenges in its prevention and control. The national burden assessment remains as a task which relies on statistical models in many developing countries, including India, due to cancer not being a notifiable disease. This study quantifies the cancer burden in India for 2016, adjusted mortality to incidence (AMI) ratio and projections for 2021 and 2025 from the National Cancer Registry Program (NCRP) and other publicly available data sources.

METHODS: Primary data on cancer incidence and mortality between 2012 and 2016 from 28 Population Based Cancer Registries (PBCRs), all-cause mortality from Sample Registration Systems (SRS) 2012-16, lifetables and disability weight from World Health Organization (WHO), the population from Census of India and cancer prevalence using the WHO-DisMod-II tool were used for this study. The AMI ratio was estimated using the Markov Chain Monte Carlo method from longitudinal NCRP-PBCR data (2001-16). The burden was quantified at national and sub-national levels as crude incidence, mortality, Years of Life Lost (YLLs), Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). The projections for the years 2021 and 2025 were done by the negative binomial regression model using STATA.

RESULTS: The projected cancer burden in India for 2021 was 26.7 million DALYs_AMI and expected to increase to 29.8 million in 2025. The highest burden was in the north (2408 DALYs_AMI per 100,000) and northeastern (2177 DALYs_AMI per 100,000) regions of the country and higher among males. More than 40% of the total cancer burden was contributed by the seven leading cancer sites - lung (10.6%), breast (10.5%), oesophagus (5.8%), mouth (5.7%), stomach (5.2%), liver (4.6%), and cervix uteri (4.3%).

CONCLUSIONS: This study demonstrates the use of reliable data sources and DisMod-II tools that adhere to the international standard for assessment of national and sub-national cancer burden. A wide heterogeneity in leading cancer sites was observed within India by age and sex. The results also highlight the need to focus on non-leading sites of cancer by age and sex. These findings can guide policymakers to plan focused approaches towards monitoring efforts on cancer prevention and control. The study simplifies the methodology used for arriving at the burden estimates and thus, encourages researchers across the world to take up similar assessments with the available data.

PMID:35546232 | PMC:PMC9092762 | DOI:10.1186/s12885-022-09578-1

Nutr J. 2022 May 11;21(1):27. doi: 10.1186/s12937-022-00778-w.

ABSTRACT

BACKGROUND: Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies.

METHODS: Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg's/Egger's test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity.

RESULTS: All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76-0.94), flavones (OR = 0.85, 95% CI: 0.77-0.95) and isoflavones (OR = 0.87, 95% CI: 0.82-0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02-1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03-1.50) and flavanones (OR = 1.31, 95% CI: 1.09-1.57).

CONCLUSIONS: The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent.

TRIAL REGISTRATION: This protocol has been registered on PROSPERO with registration number CRD42020200720 .

PMID:35545772 | PMC:PMC9092883 | DOI:10.1186/s12937-022-00778-w

BMC Genomics. 2022 May 11;23(Suppl 4):362. doi: 10.1186/s12864-022-08580-y.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a debilitating immune-mediated disease of the central nervous system that affects over 2 million people worldwide, resulting in a heavy burden to families and entire communities. Understanding the genetic basis underlying MS could help decipher the pathogenesis and shed light on MS treatment. We refined a recently developed Bayesian framework, Integrative Risk Gene Selector (iRIGS), to prioritize risk genes associated with MS by integrating the summary statistics from the largest GWAS to date (n = 115,803), various genomic features, and gene-gene closeness.

RESULTS: We identified 163 MS-associated prioritized risk genes (MS-PRGenes) through the Bayesian framework. We replicated 35 MS-PRGenes through two-sample Mendelian randomization (2SMR) approach by integrating data from GWAS and Genotype-Tissue Expression (GTEx) expression quantitative trait loci (eQTL) of 19 tissues. We demonstrated that MS-PRGenes had more substantial deleterious effects and disease risk. Moreover, single-cell enrichment analysis indicated MS-PRGenes were more enriched in activated macrophages and microglia macrophages than non-activated ones in control samples. Biological and drug enrichment analyses highlighted inflammatory signaling pathways.

CONCLUSIONS: In summary, we predicted and validated a high-confidence MS risk gene set from diverse genomic, epigenomic, eQTL, single-cell, and drug data. The MS-PRGenes could further serve as a benchmark of MS GWAS risk genes for future validation or genetic studies.

PMID:35545758 | PMC:PMC9092676 | DOI:10.1186/s12864-022-08580-y

PLoS One. 2022 May 11;17(5):e0265881. doi: 10.1371/journal.pone.0265881. eCollection 2022.

ABSTRACT

INTRODUCTION: Cervix, breast and oral cancers account for about one-third of all cancers in India which as a group is a major contributor to all non-communicable disease-related morbidity and mortality among women. Existing evidence suggests that early diagnosis plays a pivotal role in the prevention and intervention of these cancers, and many community-based early screening and awareness programs have been in place in developed countries. Currently, there is not enough research evidence regarding the sociodemographic correlates of cervix, breast and oral cancer screening among Indian women. In the present study, we aimed to assess the self-reported percentage and sociodemographic factors associated with the use of these three types of cancer screening services among Indian women aged 15-49 years.

METHODS: Data were collected from National Family Health Survey conducted during 2015-16. Sample population was 699,686 women aged 15-49 years. Associations between self-reported cervical, breast and oral cancer screening status and the associated sociodemographic factors were analyzed using multivariable logistic regression methods.

RESULTS: The percentage of screening for cervical (21%), breast (8.95%), and oral cancers (13.45%) varied significantly across the population sub-groups. Higher age, urban residence, higher education, having employment, health insurance, use of electronic media, higher household wealth quintile, having healthcare autonomy, showed a positive effect on taking screening services. Further analyses revealed that the strength of the associations varied considerably between urban and rural residents, denoting the need for region-specific intervention strategies. Sex of household head, age, watching TV, using radio, and having health insurance were the most significant contributors to the outcome effects.

CONCLUSIONS: The present study provides important insights regarding the current scenario of seeking cancer screening services among women in India. These findings could inform policy analysis and make an avenue for further in-depth analysis for future studies. Our findings conclude that cancer prevention policies should focus on leveraging the positive effects of better socioeconomic status, employment, health insurance ownership, exposure to electronic media, and better healthcare autonomy to improve the cancer screening service uptake among Indian women.

PMID:35544475 | PMC:PMC9094566 | DOI:10.1371/journal.pone.0265881

BMC Womens Health. 2022 May 10;22(1):148. doi: 10.1186/s12905-022-01743-9.

ABSTRACT

BACKGROUND: Women living with Human Immunodeficiency Virus (HIV) are at a high risk for early development of cervical cancer. Adherence to cervical cancer prevention strategies in this population is vital for the early detection and treatment of cervical cancer. This study aimed to determine the prevalence and factors associated with cervical cancer screening among HIV-positive women attending an urban HIV care center in Uganda.

METHODS: This cross-sectional study included 205 HIV-positive women receiving care at an urban HIV care center. An interviewer-administered questionnaire was used to capture sociodemographic information, history of screening for cervical cancer, and reproductive health characteristics. Logistic regression analysis was used to determine the factors associated with cervical cancer screening.

RESULTS: Of the 205 HIV-positive women with a mean age of 37.5 ± 8.87 that participated in the study, majority (n = 201, 98%) were aware of cervical cancer screening. Ninety participants (44%) had ever been screened for cervical cancer and only 33 (16.1%) had been screened in the past year. Obtaining information about cancer of the cervix and cervical cancer screening from health care professionals was significantly associated with higher levels of cervical cancer screening (adjusted odds ratio = 5.61, 95% confidence interval: 2.50-12.61, p value < 0.001).

CONCLUSION: This study highlights the low prevalence of cervical cancer screening among HIV-positive women and underscores the role of health professionals as an effective source of information on cervical cancer and cervical cancer screening. Patient education programs in HIV prevention and care facilities should emphasize cervical cancer screening messages to enhance the uptake of screening services.

PMID:35538482 | PMC:PMC9092766 | DOI:10.1186/s12905-022-01743-9

Aging (Albany NY). 2022 May 10;14(9):3989-3999. doi: 10.18632/aging.204060. Epub 2022 May 10.

ABSTRACT

While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.

PMID:35537781 | DOI:10.18632/aging.204060

Clin Lab. 2022 May 1;68(5). doi: 10.7754/Clin.Lab.2021.210459.

ABSTRACT

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs.

METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group.

RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05).

CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

PMID:35536091 | DOI:10.7754/Clin.Lab.2021.210459

Comput Math Methods Med. 2022 Apr 28;2022:8367395. doi: 10.1155/2022/8367395. eCollection 2022.

ABSTRACT

This study investigated the expression of some frequently used immunohistochemistry (IHC) markers. Besides, we evaluated their correlations with the clinical features and outcomes of intrahepatic cholangiocarcinoma (ICC). Patients who underwent surgical removal of the ICC tumors were followed up for 4 years. The paraffin-embedded sections were used to obtain different markers, including CK7, CK19, CK20, CDX2, Glypican3, Hepa1, Ki-67, Villin, and SATB1. Overall survival in relation to IHC marker expression patterns and other clinical characteristics was evaluated by Kaplan-Meier survival curve and log-rank test, followed by the Cox proportional hazard model (to evaluate the relationship between multiple factors and the overall postoperative survival). A total of 122 ICC patients (67 males and 55 females, averagely aged 57.75) were included in this study. There were 44 cases with vascular invasion, 46 cases with lymphatic metastasis, and 13 cases with distant metastasis. CK7 was negatively correlated with lymphatic metastasis; and in distant-metastasis cases, the positive ratio of SATB1 was lower. Interestingly, SATB1 expression indicated a poorer survival, while Villin expression was associated with a better survival. The COX regression analysis showed that female was a protective factor versus male, Villin expression was a strong protective factor, and Ki-67 expression was correlated with a poor survival. Together, IHC markers are associated with tumor features and postoperative survival, especially for SATB1 as a risk factor and Villin as a protective marker, and female ICC patients may have better survival than males.

PMID:35529254 | PMC:PMC9071873 | DOI:10.1155/2022/8367395

Prev Med. 2022 Jun;159:107075. doi: 10.1016/j.ypmed.2022.107075. Epub 2022 May 6.

ABSTRACT

Advances in knowledge about breast cancer risk factors have led to the development of more comprehensive risk models. These integrate information on a variety of risk factors such as lifestyle, genetics, family history, and breast density. These risk models have the potential to deliver more personalised breast cancer prevention. This is through improving accuracy of risk estimates, enabling more effective targeting of preventive options and creating novel prevention pathways through enabling risk estimation in a wider variety of populations than currently possible. The systematic use of risk tools as part of population screening programmes is one such example. A clear understanding of how such tools can contribute to the goal of personalised prevention can aid in understanding and addressing barriers to implementation. In this paper we describe how emerging models, and their associated tools can contribute to the goal of personalised healthcare for breast cancer through health promotion, early disease detection (screening) and improved management of women at higher risk of disease. We outline how addressing specific challenges on the level of communication, evidence, evaluation, regulation, and acceptance, can facilitate implementation and uptake.

PMID:35526672 | DOI:10.1016/j.ypmed.2022.107075

J Exp Clin Cancer Res. 2022 May 7;41(1):169. doi: 10.1186/s13046-022-02375-5.

ABSTRACT

BACKGROUND: Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer because of its aggressive biological characteristics and no effective targeted agents. However, the mechanism underlying its aggressive behavior remain poorly understood. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) overexpression occurs specifically in BLBC. Here, we studied the possible molecular mechanisms of B3GBT5 promoting the aggressiveness of BLBC.

METHODS: The potential effects of B3GNT5 on breast cancer cells were tested by colony formation, mammosphere formation, cell proliferation assay, flow cytometry and Western blotting. The glycosylation patterns of B3GNT5 and associated functions were determined by Western blotting, quantitative real-time PCR and flow cytometry. The effect of B3GNT5 expression on BLBC was assessed by in vitro and in vivo tumorigenesis model.

RESULTS: In this study, we showed that B3GNT5 copy number amplification and hypomethylation of B3GNT5 promoter contributed to the overexpression of B3GNT5 in BLBC. Knockout of B3GNT5 strongly reduced surface expression of SSEA-1 and impeded cancer stem cell (CSC)-like properties of BLBC cells. Our results also showed that B3GNT5 protein was heavily N-glycosylated, which is critical for its protein stabilization. Clinically, elevated expression of B3GNT5 was correlated with high grade, large tumor size and poor survival, indicating poor prognosis of breast cancer patients.

CONCLUSIONS: Our work uncovers the critical association of B3GNT5 overexpression and glycosylation with enhanced CSCs properties in BLBC. These findings suggest that B3GNT5 has the potential to become a prognostic marker and therapeutic target for BLBC.

PMID:35526049 | PMC:PMC9077843 | DOI:10.1186/s13046-022-02375-5

BMC Public Health. 2022 May 7;22(1):912. doi: 10.1186/s12889-022-13262-1.

ABSTRACT

BACKGROUND: Areca nut (AN) is an addictive substance consumed in the Southeast region and is highly associated with oral premalignant lesions and oral cancer. The impact of AN use in the United States (US) is largely unknown, but the products are readily available and probably used by a significant fraction of Asian immigrants or descendants living in the US. We aimed at assessing AN use prevalence among the Asian community in Houston, Texas.

METHODS: A cross-sectional questionnaire was used to interview adult individuals (≥ 18 years of age) who self-identified as Asian immigrants or descendants residing in Houston. Means, frequencies, and proportions were reported. Factors associated with AN use were evaluated using logistic regression.

RESULTS: We surveyed 275 individuals (58% women, 43% between 35-54 years old, 67% born outside of the US, and 6% concurrent smokers). Among respondents, 91% were familiar with AN products, 17% self-reported ever use of AN products in the US, and 31% had friends/family members who were AN ever users. AN use was significantly associated with being Indian Subcontinent immigrants or descendants (ISID) (OR = 3·9; CI: 1·10,13·81; p = 0·035) and having friends/family members using AN products (OR = 6·2; CI: 1·69, 22·69; p = 0·006).

CONCLUSIONS: Our findings provide quantitative data on the prevalence of AN ever use and context for future AN prevention and cessation interventions specific to the Southeast Asian groups living in the US mainland. This is crucial for the prevention and control of oral cancer and other detrimental conditions related to AN consumption.

PMID:35525926 | PMC:PMC9078632 | DOI:10.1186/s12889-022-13262-1

BMC Cancer. 2022 May 7;22(1):514. doi: 10.1186/s12885-022-09592-3.

ABSTRACT

OBJECTIVE: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the current standard of care for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. However, the optimal strategy for elderly NSCLC patients is still under debate. This study was designed to explore the optimal first-line regimens by comparing diverse strategies for elderly and non-elderly EGFR-mutated NSCLC patients.

METHODS: A systematic review was conducted to summarize all available randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Central Register of Controlled Trials databases, and international conferences before September 30, 2020. The primary outcome was progression free survival (PFS), and the secondary outcome was overall survival (OS). A network meta-analysis (NMA) was constructed using the Bayesian statistical model to synthesize the survival outcomes of all the treatments.

RESULTS: In total, 12 RCTs were deemed eligible for inclusion with 3779 patients who have received 10 diverse treatments including EGFR-TKIs. Results from the Bayesian ranking suggested that osimertinib was most likely to rank the first in overall population and in elderly patients in PFS, with the cumulative probabilities of 42.20% and 31.46%, respectively. In non-elderly group (younger than 65 years old), standard of care (SoC, representing first-generation EGFR-TKIs in this NMA) + chemotherapy ranked the first (31.66%). As for OS, SoC + chemotherapy ranked first in all patients (64.33%), patients younger than 65 years old (61.98%), or older than 65 years old (34.45%).

CONCLUSION: The regimen of osimertinib is associated with the most favorable PFS in elderly advanced EGFR-mutated NSCLC patients, while SoC + chemotherapy is the optimal strategy in PFS for non-elderly NSCLC patients harboring EGFR activating mutations, and in OS for both elderly and non-elderly EGFR-mutated advanced NSCLC patients.

TRIAL REGISTRATION: INPLASY protocol 2020100061 https://doi.org/10.37766/inplasy2020.20.0061 .

PMID:35525919 | PMC:PMC9077975 | DOI:10.1186/s12885-022-09592-3

Cell Death Dis. 2022 May 6;13(5):441. doi: 10.1038/s41419-022-04882-x.

ABSTRACT

As a widely studied adoptive treatment method, CIK (cytokine-induced killer cells) treatment has shown clinical benefits in many clinical trials on non-small cell lung cancer. As a heterogeneous cell population, however, CIK cells have a strong instability and individual differences in their efficacies, which are collaboratively regulated by the tumor microenvironment and CIK subpopulations. Among them, CD4⁺ T cells belong to a crucial subgroup of the CIK cell population, and their influence on CIK therapy is still unclear. Herein, we show how CD4⁺ T cells positively regulate the functions of CD3⁺CD56⁺ T and CD3⁺CD8⁺ T cells. During this process, we found that Th1/Th17 CD4⁺ subgroups can induce the phosphorylation of the AKT pathway by secreting IL-17A, and upregulate the expression of T-bet/Eomes transcription factors, thereby restoring the function of CD8⁺/CD3⁺CD56⁺ T cells and reversing the exhaustion of PD-1⁺Tim-3⁺ T cells. These findings will provide guidance for the clinical screening of suitable populations for CIK treatment and formulation of strategies for CIK therapy plus immune checkpoint treatment. Based on these findings, we are conducting an open-label phase II study (NCT04836728) is to evaluate the effects of autologous CIKs in combination with PD-1 inhibitor in the first-line treatment of IV NSCLC, and hope to observe patients' benefits in this clinical trial.

PMID:35523765 | PMC:PMC9076680 | DOI:10.1038/s41419-022-04882-x

Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-16. doi: 10.1200/EDBK_350241.

ABSTRACT

By 2030, early-onset colorectal cancer (EOCRC) is expected to become the leading cancer-related cause of death for people age 20 to 49. To improve understanding of this phenomenon, we analyzed the geographic determinants of EOCRC in Utah by examining county-level incidence and mortality. We linked data from the Utah Population Database to the Utah Cancer Registry to identify residents (age 18-49) diagnosed with EOCRC between 2000 and 2020, and we used spatial empirical Bayes smoothing to determine county-level hotspots. We identified 1,867 EOCRC diagnoses (52.7% in male patients, 69.2% in non-Hispanic White patients). Ten counties (34%) were classified as hotspots, with high EOCRC incidence or mortality. Hotspot status was unrelated to incidence rates, but non-Hispanic ethnic-minority men (incidence rate ratio, 1.49; 95% CI, 1.15-1.91), Hispanic White men and women (incidence rate ratio, 2.24; 95% CI, 2.00-2.51), and Hispanic ethnic-minority men and women (incidence rate ratio, 4.59; 95% CI, 3.50-5.91) were more likely to be diagnosed with EOCRC. After adjustment for income and obesity, adults living in hotspots had a 31% higher hazard for death (HR, 1.31; 95% CI, 1.02-1.69). Survival was poorest for adults with a late-stage diagnosis living in hotspots (chi square (1) = 4.0; p = .045). Adults who were married or who had a life partner had a lower hazard for death than single adults (HR, 0.73; 95% CI, 0.58-0.92). The risk for EOCRC is elevated in 34% of Utah counties, warranting future research and interventions aimed at increasing screening and survival in the population age 18 to 49.

PMID:35522914 | DOI:10.1200/EDBK_350241

Oncologist. 2022 May 6;27(5):363-370. doi: 10.1093/oncolo/oyac030.

ABSTRACT

BACKGROUND: Adolescent and young adult (AYA) patients with cancer are underrepresented on cancer clinical trials (CCTs), and most AYAs are treated in the community setting. Past research has focused on individual academic institutions, but factors impacting enrollment vary across institutions. Therefore, we examined the patterns of barriers and facilitators between high- and low-AYA enrolling community-based clinics to identify targets for intervention.

MATERIALS AND METHODS: We conducted 34 semi-structured interviews with stakeholders employed used at National Cancer Institute Community Oncology Research Program (NCORP) affiliate sites ("clinics"). Stakeholders (eg, clinical research associates, patient advocates) were recruited from high- and low-AYA enrolling clinics. We conducted a content analysis and calculated the percentage of stakeholders from each clinic type that reported the barrier or facilitator. A 10% gap between high- and low-enrollers was considered the threshold for differences.

RESULTS: Both high- and low-enrollers highlighted insufficient resources as a barrier and the presence of a patient eligibility screening process as a facilitator to AYA enrollment. High-enrolling clinics reported physician gatekeeping as a barrier and the improvement of departmental collaboration as a facilitator. Low-enrollers reported AYAs' uncertainty regarding the CCT process as a barrier and the need for increased physician endorsement of CCTs as a facilitator.

CONCLUSIONS: High-enrolling clinics reported more barriers downstream in the enrollment process, such as physician gatekeeping. In contrast, low-enrolling clinics struggled with the earlier steps in the CCT enrollment process, such as identifying eligible trials. These findings highlight the need for multi-level, tailored interventions rather than a "one-size-fits-all" approach to improve AYA enrollment in the community setting.

PMID:35522559 | PMC:PMC9074986 | DOI:10.1093/oncolo/oyac030

BMC Med. 2022 May 6;20(1):155. doi: 10.1186/s12916-022-02357-6.

ABSTRACT

BACKGROUND: Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/β, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC.

METHODS: Patients aged 18-75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m², p.o., bid, on day 1-14 every 21 days), oxaliplatin (130 mg/m², i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1-14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety.

RESULTS: Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7-90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9-99.2). At a median follow-up of 14.1 months (95% CI, 9.9-18.3), median PFS was 11.3 months (95% CI, 7.1-14.1), and DOR was 7.9 months (95% CI, 5.5-12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays.

CONCLUSIONS: Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles.

TRIAL REGISTRATION: ClinicalTrials.gov : NCT04080843.

PMID:35513832 | PMC:PMC9071922 | DOI:10.1186/s12916-022-02357-6

Methods Mol Biol. 2022;2469:219-229. doi: 10.1007/978-1-0716-2185-1_18.

ABSTRACT

Glucosinolates (GLSs) are a group of plant secondary metabolites mainly found in Cruciferous plants. The main hydrolysis products of GLSs, isothiocyanates (ITCs), are the bioactive metabolites that have shown plant defense and human cancer prevention properties. Untargeted metabolomic analysis of plant metabolites can uncover the profiles of these bioactive phytochemicals in specific plants and discover potential human health promoting products. We have developed an integrated metabolomic analysis method for plant samples, with specific focus on nonvolatile GLSs and volatile ITCs. In this chapter, we describe in detail the protocols, including metabolite extraction, high resolution LC-MS and GC-MS analysis, and data processing. The method is readily applicable to untargeted analysis of other nonvolatile and volatile metabolites in plants.

PMID:35508842 | DOI:10.1007/978-1-0716-2185-1_18

Cell Death Dis. 2022 May 4;13(5):434. doi: 10.1038/s41419-022-04853-2.

ABSTRACT

As a critical member of the ubiquitin-specific proteolytic enzyme family, ubiquitin-specific peptidase 20 (USP20) regulates the stability of proteins via multiple signaling pathways. In addition, USP20 upregulation is associated with various cellular biological processes, such as cell cycle progression, proliferation, migration, and invasion. Emerging studies have revealed the pivotal role of USP20 in the tumorigenesis of various cancer types, such as breast cancer, colon cancer, lung cancer, gastric cancer and adult T cell leukemia. In our review, we highlight the different mechanisms of USP20 in various tumor types and demonstrate that USP20 regulates the stability of multiple proteins. Therefore, regulating the activity of USP20 is a novel tumor treatment. However, the clinical significance of USP20 in cancer treatment merits more evidence. Finally, different prospects exist for the continued research focus of USP20.

PMID:35508480 | PMC:PMC9068925 | DOI:10.1038/s41419-022-04853-2

BMJ Open. 2022 May 4;12(5):e058635. doi: 10.1136/bmjopen-2021-058635.

ABSTRACT

OBJECTIVES: The introduction of primary Human Papillomavirus (HPV) testing in the National Health Service (NHS) Cervical Screening Programme in England means the screening interval for 25-49 years can be extended from 3 to 5 years. We explored women's responses to the proposed interval extension.

METHODS: We conducted semi-structured phone/video interviews with 22 women aged 25-49 years. Participants were selected to vary in age, socioeconomics and screening history. We explored attitudes to the current 3-year interval, then acceptability of a 5-year interval. Interviews were transcribed verbatim and analysed using framework analysis.

RESULTS: Attitudes to the current 3-year interval varied; some wanted more frequent screening, believing cancer develops quickly. Some participants worried about the proposed change; others trusted it was evidence based. Frequent questions concerned the rationale and safety of longer intervals, speed of cancer development, the possibility of HPV being missed or cell changes occurring between screens. Many participants felt reassured when the interval change was explained alongside the move to HPV primary screening, of which most had previously been unaware.

CONCLUSIONS: Communication of the interval change should be done in the context of broader information about HPV primary screening, emphasising that people who test negative for HPV are at lower risk of cell changes so can safely be screened every 5 years. The long time needed for HPV to develop into cervical cancer provides reassurance about safety, but it is important to be transparent that no screening test is perfect.

PMID:35508345 | PMC:PMC9073390 | DOI:10.1136/bmjopen-2021-058635