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Trends in Endocrinology and Metabolism:... Aug 2023Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects.... (Review)
Review
Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects. However, radiation causes healthy tissue toxicity as a side effect. In intra-abdominal and pelvic malignancies, the healthy bowel is inevitably included in the radiation field, causing radiation-induced enteritis and dramatically affecting the gut microbiome. This condition is associated with significant morbidity and mortality that impairs cancer patients' and survivors' quality of life. This Review provides a critical overview of the main drivers in modulating the gut microenvironment in homeostasis, disease, and injury, focusing on gut microbial metabolites and microorganisms that influence epithelial regeneration upon radiation injury.
Topics: Humans; Gastrointestinal Microbiome; Quality of Life; Enteritis; Radiation Injuries; Neoplasms; Regeneration; Tumor Microenvironment
PubMed: 37336645
DOI: 10.1016/j.tem.2023.05.006 -
JAMA Oncology Oct 2023Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and...
The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.
IMPORTANCE
Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.
OBJECTIVE
To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.
EVIDENCE REVIEW
The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.
FINDINGS
In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.
CONCLUSIONS AND RELEVANCE
In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Topics: Adult; Female; Humans; Male; Global Burden of Disease; Global Health; Incidence; Lip; Pharyngeal Neoplasms; Quality-Adjusted Life Years; Risk Factors; Tobacco Use
PubMed: 37676656
DOI: 10.1001/jamaoncol.2023.2960 -
Journal of Applied Clinical Medical... Dec 2023To probe the differences of dosimetry and acute radiation enteritis between prone and supine position in gynecological cancer patients treated with intensity-modulate...
PURPOSE
To probe the differences of dosimetry and acute radiation enteritis between prone and supine position in gynecological cancer patients treated with intensity-modulate radiotherapy (IMRT).
METHODS
Gynecologic tumor patients who received IMRT from January 2020 to July 2021 were analyzed. 60 patients were enrolled and divided into the supine or prone position group according to different radiotherapy positions, including 34 patients in prone position and 26 patients in supine position. The dose-volume histogram of organs at risk (OARs) and the incidence of acute radiation enteritis were compared between the two groups. Multivariate logistic regression analysis was conducted to show the clinical characteristics and dose volume metrics to the association of acute radiation enteritis.
RESULTS
The percentage of volume receiving 5 Gy, 10 Gy, 15 Gy, 20 Gy, 30 Gy, 40 Gy, and 45 Gy doses for the small intestine were 79.0%, 67.4%, 59.6%, 44.3%, 17.0%, 8.9%, and 6.0%, respectively in the prone group, which were lower than those in the supine group (P < 0.05). The mean radiation dose (D ) of the small intestine exposure in prone group was decreased (P < 0.001). Compared with the supine group, the prone group who suffered from acute radiation enteritis were much less. The probability of indigestion, nausea, vomiting, diarrhea, and abdominal pain in the prone position were 35.29%, 29.41%, 17.65%, 38.24%, and 5.88%, respectively. The differences in indigestion, nausea, and diarrhea between the two groups were statistically significant (P = 0.012, P = 0.029, and P = 0.041). Multivariate logistic regression analysis was shown that prone position was found to be protective against indigestion (P = 0.002), nausea (P = 0.013), vomiting (P = 0.035), and abdominal pain (P = 0.021).
CONCLUSION
Prone position in IMRT for gynecological cancers could significantly reduce radiation dose to the small bowel and colon, which would decrease the occurrence and severity of acute intestinal side effects possibly.
Topics: Humans; Female; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Supine Position; Dyspepsia; Prone Position; Enteritis; Radiotherapy Planning, Computer-Assisted; Genital Neoplasms, Female; Diarrhea; Abdominal Pain; Nausea; Vomiting
PubMed: 37621141
DOI: 10.1002/acm2.14135 -
Gut Microbes Dec 2023Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. () is a recently...
Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. () is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of . Together, our results demonstrated that plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.
Topics: Humans; Mice; Animals; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Intestines; Verrucomicrobia; Metformin
PubMed: 38087436
DOI: 10.1080/19490976.2023.2293312 -
Frontiers in Immunology 2023Gastrointestinal inflammation and bleeding are commonly induced by cancer radiotherapy and chemotherapy but mechanisms are unclear. We demonstrated an increased number...
Gastrointestinal inflammation and bleeding are commonly induced by cancer radiotherapy and chemotherapy but mechanisms are unclear. We demonstrated an increased number of infiltrating heme oxygenase-1 positive (HO-1+) macrophages (Mø, CD68+) and the levels of hemopexin (Hx) in human colonic biopsies from patients treated with radiation or chemoradiation versus non-irradiated controls or in the ischemic intestine compared to matched normal tissues. The presence of rectal bleeding in these patients was also correlated with higher HO-1+ cell infiltration. To functionally assess the role of free heme released in the gut, we employed myeloid-specific HO-1 knockout (), hemopexin knockout () and control mice. Using conditional knockout (KO) mice, we showed that a deficiency of HO-1 in myeloid cells led to high levels of DNA damage and proliferation in colonic epithelial cells in response to phenylhydrazine (PHZ)-induced hemolysis. We found higher levels of free heme in plasma, epithelial DNA damage, inflammation, and low epithelial cell proliferation in mice after PHZ treatment compared to wild-type mice. Colonic damage was partially attenuated by recombinant Hx administration. Deficiency in or did not alter the response to doxorubicin. Interestingly, the lack of Hx augmented abdominal radiation-mediated hemolysis and DNA damage in the colon. Mechanistically, we found an altered growth of human colonic epithelial cells (HCoEpiC) treated with heme, corresponding to an increase in mRNA levels and heme:G-quadruplex complexes-regulated genes such as , and Heme-treated HCoEpiC cells exhibited growth advantage in the absence or presence of doxorubicin, in contrast to poor survival of heme-stimulated RAW247.6 Mø. In summary, our data indicate that accumulation of heme in the colon following hemolysis and/or exposure to genotoxic stress amplifies DNA damage, abnormal proliferation of epithelial cells, and inflammation as a potential etiology for gastrointestinal syndrome (GIS).
Topics: Mice; Humans; Animals; Heme; Hemolysis; Hemopexin; Mice, Knockout; Inflammation; Doxorubicin; Colon
PubMed: 37342339
DOI: 10.3389/fimmu.2023.1184105 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To explore the relationship between gut microbiota and chronic radiation enteritis of cervical cancer patients.
OBJECTIVE
To explore the relationship between gut microbiota and chronic radiation enteritis of cervical cancer patients.
METHODS
Fecal samples were collected from 34 patients with cervical cancer who had received radiotherapy for at least 6 months but less than 2 years. The patients were divi-ded into mild toxicity group (mild, M) with no symptoms or mild symptoms and severe toxicity group (severe, S) with severe symptoms by clinical diagnosis of radiation enteritis, modified inflammatory bo-wel disease questionnaire (IBDQ) and Vaizey questionnaire. DNA extracted from fecal samples was sequenced and analyzed by 16S rRNA sequencing method. The analysis indexes included α-diversity, β-diversity, taxonomic composition analysis, taxonomic hierarchy tree and linear discriminant analysis (LDA) effect size (LEfSe).
RESULTS
From the perspective of species diversity, most indices of α diversity in group M were higher than those in group S. Although there was no significant difference, it also indicated a correlation between low species diversity and severity of intestinal symptoms to some extent. There was also a significant difference in the distribution of β diversity between the two groups, indicating that the microbial characteristics were different between the two groups. From the perspective of species composition, the M group had higher Firmicutes [66.5% (M) . 56.0% (S)] and lower Proteobacteria [4.1% (M) . 13.9% (S)] than the S group at the level of phyla. At the level of genus, there were also significant differences between the two groups: [2.7% (M) . 8.5% (S)], [7.0% (M) . 2.7% (S)], Lachnospiraceae_ [1.3% (M) . 4.7% (S)]. Through LEfSe also found some species with statistically significant differences between the two groups. The abundance of and in group M was significantly higher, while the abundance of Veillonellaceae, Rhodobacteraceae, and Rhodobacterales in group S was significantly higher. The taxonomic hierarchy tree also intuitively showed the difference in species composition between the two groups at each taxonomic level in space.
CONCLUSION
The severity of chronic radiation enteritis of cervical cancer is closely related to the characteristics and composition of gut microbiota.
Topics: Female; Humans; Gastrointestinal Microbiome; Bacteria; Uterine Cervical Neoplasms; RNA, Ribosomal, 16S; Enteritis; Inflammatory Bowel Diseases; Radiation Injuries
PubMed: 37534641
DOI: 10.19723/j.issn.1671-167X.2023.04.008