scholarly journals Urinary metabolites as indicators of human exposure to chemical carcinogens

2021 ◽  
Vol 50 (4) ◽  
pp. 21-42
Author(s):  
Vladan Radosavljević
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Bladder Cancer ◽  
Dairy Products ◽  
Public Health Problem ◽  
Inorganic Arsenic ◽  
Urinary Metabolites ◽  
Population Exposure ◽  
Chemical Carcinogens ◽  
Nasal Sinus

Population exposure to environmental chemical carcinogens is a growing public health problem. Carcinogenic chemicals may be classified into two groups: genotoxic and non-genotoxic. A genotoxic chemical has a potential to induce the development of cancer, either in direct interaction with DNA or with cell structures, which are responsible for the maintenance of genome integrity. A non-genotoxic chemical has a potential to induce cancer indirectly by entering the processes of cancer etiopathogenesis. Previous research studies indicate that inorganic arsenic compounds may be associated with various malign diseases (lung cancer, urinary bladder cancer, skin, kidney, liver and prostate cancer). Inorganic arsenic is mainly present in meat, dairy products and grains, while organic arsenic (arsenobetaine) is present in seafood, fruit and vegetables. Benzene metabolites are associated with different types of leukemias and lymphomas, benzidine with bladder cancer, nickel with lung cancer, chromium compounds with lung cancer, nose and nasal sinus cancer. The greatest occupational exposure to benzene is in industry (leather, electronic device, shoes, sports equipment), while people may come into contact with benzidine through consumer goods (leather products, clothes, toys). The highest concentrations of nickel were measured in the beans, walnuts and grains. Cadmium and cadmium compounds cause lung cancer, and influence the occurrence of renal and prostate cancer. The risk of hepatocellular carcinoma is significantly increased in respondents with high concentrations of urinary metabolites of aflatoxin (aflatoxin N7-gvanine adducts). Lindane isomers are present in dairy products, meat, fish, poultry, garden fruit, oils and lipids, leaf and root vegetables and sugar, and they cause non-Hodgkin lymphoma. There is a positive correlation between the consumption of Aristolochia plants and the occurrence of urothelial carcinoma. There are no screening examinations for the identification of persons who are at great risk of developing malign disease in the next 10 or 20 years. As for the prevention of malign diseases, it is necessary to put an accent on finding the adequate methods for determining the concentrations of urinary metabolites for toxic chemical carcinogens and define their risk values.

scholarly journals Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junyu Long ◽  
Dongxu Wang ◽  
Xu Yang ◽  
Anqiang Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Esophagogastric Cancer ◽  
Clinical Benefits

Abstract Background Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. Methods We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. Results We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. Conclusions Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

scholarly journals Racial Differences in Incident Genitourinary Cancer Cases Captured in the National Cancer Database

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 671
Author(s):  
Dylan T. Wolff ◽  
Thomas F. Monaghan ◽  
Danielle J. Gordon ◽  
Kyle P. Michelson ◽  
Tashzna Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Bladder Cancer ◽  
Kidney Cancer ◽  
The United States ◽  
Coverage Rate ◽  
National Cancer Database ◽  
Genitourinary Cancer ◽  
Coverage Rates ◽  
Capture Rates

Background and Objectives: The National Cancer Database (NCDB) captures nearly 70% of all new cancer diagnoses in the United States, but there exists significant variation in this capture rate based on primary tumor location and other patient demographic factors. Prostate cancer has the lowest coverage rate of all major cancers, and other genitourinary malignancies likewise fall below the average NCDB case coverage rate. We aimed to explore NCDB coverage rates for patients with genitourinary cancers as a function of race. Materials and Methods: We compared the incidence of cancer cases in the NCDB with contemporary United States Cancer Statistics data. Results: Across all malignancies, American Indian/Alaskan Natives subjects demonstrated the lowest capture rates, and Asian/Pacific Islander subjects exhibited the second-lowest capture rates. Between White and Black subjects, capture rates were significantly higher for White subjects overall and for prostate cancer and kidney cancer in White males, but significantly higher for bladder cancer in Black versus White females. No significant differences were observed in coverage rates for kidney cancer in females, bladder cancer in males, penile cancer, or testicular cancer in White versus Black patients. Conclusions: Differential access to Commission on Cancer-accredited treatment facilities for racial minorities with genitourinary cancer constitutes a unique avenue for health equity research.

Lung Cancer in Brazil

2012 ◽  
pp. 426-431
Author(s):  
Gilberto Schwartsmann
Keyword(s):  
Lung Cancer ◽  
Cause Of Death ◽  
Public Health Problem ◽  
Lung Cancer Mortality ◽  
World Health ◽  
Cancer Type ◽  
Positive Effects ◽  
Incident Cancer ◽  
Health Organization ◽  
Tremendous Challenge

Overview: Cancer is now the second leading cause of death in Brazil (after cardiovascular diseases) and a public health problem, with around 500,000 new cases in 2012. Excluding nonmelanoma skin cancer, lung cancer is the second most incident cancer type in men, with 17,210 expected new cases. In women, it is the fifth most incident cancer, with 10,110 expected new cases. The estimated age-adjusted lung cancer mortality rate is about 13/100,000 for men and 5.4/100,000 for women. Lung cancer rates in men increased until the early 1990s and decreased thereafter, especially in the younger population. In contrast, a steady upward trend was observed for women. The positive effects in men were probably due to the successful anti-tobacco campaign conducted in Brazil over the last decades, which led to a decrease in the adult smoking population, from 32% in the early 1980s to 17% in the 2000s. Although the Brazilian National Cancer Institute is strongly committed to providing excellence in multimodality care to cancer patients, limitations in availability and adequate geographic distribution of specialists and well-equipped cancer centers are evident. Major disparities in patient access to proper staging and state-of-the-art treatment still exist. Considering that World Health Organization (WHO) officials estimate that cancer will become the number one cause of death in most developing countries, including Brazil, in the next decades, it is highly recommended for government authorities to implement firm actions to face this tremendous challenge.

scholarly journals Endoscopic-Ultrasound-Guided Tissue Sampling Facilitates the Detection of Local Recurrence and Extra Pelvic Metastasis in Pelvic Urologic Malignancy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ferga C. Gleeson ◽  
Jonathan E. Clain ◽  
R. Jeffrey Karnes ◽  
Elizabeth Rajan ◽  
Mark D. Topazian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bladder Cancer ◽  
Local Recurrence ◽  
Endoscopic Ultrasound ◽  
Gold Standard ◽  
Final Diagnosis ◽  
Tissue Sampling ◽  
Invasive Method ◽  
Urologic Malignancy ◽  
Sensitivity Specificity

Pelvic lymph node dissection is the gold standard for assessing nodal disease in prostate or bladder cancer and is superior to CT, MRI and PET staging. Endoscopic ultrasound (EUS) provides an alternative, less invasive method of cytohistologic material acquisition, but its performance in pelvic urologic malignancy is unknown. Therefore, our aim was to evaluate the diagnostic accuracy of EUS guided tissue sampling for these malignancies when compared to a composite cytohistologic and surgical gold standard. A median of 3 FNA passes were performed (n=19 patients) revealing a sensitivity, specificity, PPV and NPV of 94.4% (72–99), 100% (2–100), 100% (80–100) and 50% (1–98) respectively. The perirectal space was the most frequently sampled location irrespective of the primary urological cancer origin. Final diagnosis established by EUS tissue sampling included bladder cancer (n=1), bladder cancer local recurrence (n=8), bladder cancer extra pelvic metastases (n=1), prostate cancer (n=2), prostate cancer local recurrence (n=4), prostate cancer extra pelvic metastases (n=1), testicular cancer extra pelvic metastases (n=1) and a benign seminal vesicle (n=1). EUS guided sampling of the gut wall, lymph nodes, or perirectal space yields suitable diagnostic material to establish the presence of primary, local recurrence or extra pelvic metastases of pelvic urologic malignancy.

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