Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer

Endometrial cancer; Guidelines; TreatmentCàncer d'endometri; Pautes; TractamentCáncer de endometrio; Pautas; TratamientoThe most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.All costs relating to this consensus conference were covered by the ESMO and the ISMPO from central dedicated funds. There was no external funding of the event or the manuscript production

Can Global Variation of Nasopharynx Cancer Be Retrieved from the Combined Analyses of IARC Cancer Information (CIN) Databases?

BACKGROUND: The international nasopharynx cancer (NPC) burdens are masked due to the lack of integrated studies that examine epidemiological data based on up-to-date international disease databases such as the Cancer Information (CIN) databases provided by the International Agency for Research on Cancer (IARC). METHODS: By analyzing the most recently updated NPC epidemiological data available from IARC, we tried to retrieve the worldwide NPC burden and patterns from combined analysis with GLOBOCAN2008 and the Cancer Incidence in Five Continents (CI5) databases. We provide age-standardized rates (ASR) for NPC mortality in 20 highest cancer registries from GLOBOCAN2008 and the World Health Organization (WHO) mortality databases, respectively. However, NPC incidence data can not be retrieved since it is not individually listed in CI5 database. The trend of NPC mortality was investigated with Joinpoint analysis in the selected countries/regions with high ASR. RESULTS: GLOBOCAN 2008 revealed that the highest NPC incidence rates in 2008 were in registries from South-Eastern Asia, Micronesia and Southern Africa with Malaysia, Indonesia and Singapore ranking the top 3. WHO mortality database analysis revealed that China Hong Kong, Singapore and Malta ranks the top 3 regions with the highest 5-year mortality rates. CONCLUSIONS: NPC mortality rate is about 2-3 times higher in male than that in female, and shows decrease tendency in those selected countries/regions during the analyzed periods. However, the integrated analyses of the current IARC CIN databases may not be suitable to retrieve epidemiological data of NPC. Much effort is required to improve the local cancer entry and regional death-reporting systems so as to aid similar studies

Can Global Variation of Nasopharynx Cancer Be Retrieved from the Combined Analyses of IARC Cancer Information (CIN) Databases?

BACKGROUND: The international nasopharynx cancer (NPC) burdens are masked due to the lack of integrated studies that examine epidemiological data based on up-to-date international disease databases such as the Cancer Information (CIN) databases provided by the International Agency for Research on Cancer (IARC). METHODS: By analyzing the most recently updated NPC epidemiological data available from IARC, we tried to retrieve the worldwide NPC burden and patterns from combined analysis with GLOBOCAN2008 and the Cancer Incidence in Five Continents (CI5) databases. We provide age-standardized rates (ASR) for NPC mortality in 20 highest cancer registries from GLOBOCAN2008 and the World Health Organization (WHO) mortality databases, respectively. However, NPC incidence data can not be retrieved since it is not individually listed in CI5 database. The trend of NPC mortality was investigated with Joinpoint analysis in the selected countries/regions with high ASR. RESULTS: GLOBOCAN 2008 revealed that the highest NPC incidence rates in 2008 were in registries from South-Eastern Asia, Micronesia and Southern Africa with Malaysia, Indonesia and Singapore ranking the top 3. WHO mortality database analysis revealed that China Hong Kong, Singapore and Malta ranks the top 3 regions with the highest 5-year mortality rates. CONCLUSIONS: NPC mortality rate is about 2-3 times higher in male than that in female, and shows decrease tendency in those selected countries/regions during the analyzed periods. However, the integrated analyses of the current IARC CIN databases may not be suitable to retrieve epidemiological data of NPC. Much effort is required to improve the local cancer entry and regional death-reporting systems so as to aid similar studies

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

<p>Abstract</p> <p>Background</p> <p>Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of <it>Taxus cuspidata </it>(<it>TC</it>) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).</p> <p>Methods</p> <p>Components of <it>TC </it>extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA.</p> <p>Results</p> <p><it>TC </it>extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of <it>TC </it>extract <it>in vitro</it>. <it>TC </it>extract inhibited cancer cell growth by inducing apoptosis and G₂/M cell cycle arrest. Most interestingly, <it>TC </it>extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells <it>in vitro</it>, with Combination Index values (CI) ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5-FU used alone. Furthermore, <it>TC </it>extract did not affect the pharmacokinetics of 5-FU in rats.</p> <p>Conclusions</p> <p>The combinational use of the <it>TC </it>extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.</p

Case–control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk

Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg213His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case–control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens

Aqueous Cinnamon Extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential

<p>Abstract</p> <p>Background</p> <p>Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa.</p> <p>Methods</p> <p>The aqueous cinnamon extract (ACE-<it>c</it>) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-<it>c </it>was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-<it>c </it>were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-<it>c </it>treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Δψ_m) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS.</p> <p>Results</p> <p>Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-<it>c </it>exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-<it>c</it>. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential.</p> <p>Conclusion</p> <p>Cinnamon could be used as a potent chemopreventive drug in cervical cancer.</p

Multiple Pathway-Based Genetic Variations Associated with Tobacco Related Multiple Primary Neoplasms

BACKGROUND: In order to elucidate a combination of genetic alterations that drive tobacco carcinogenesis we have explored a unique model system and analytical method for an unbiased qualitative and quantitative assessment of gene-gene and gene-environment interactions. The objective of this case control study was to assess genetic predisposition in a biologically enriched clinical model system of tobacco related cancers (TRC), occurring as Multiple Primary Neoplasms (MPN). METHODS: Genotyping of 21 candidate Single Nucleotide Polymorphisms (SNP) from major metabolic pathways was performed in a cohort of 151 MPN cases and 210 cancer-free controls. Statistical analysis using logistic regression and Multifactor Dimensionality Reduction (MDR) analysis was performed for studying higher order interactions among various SNPs and tobacco habit. RESULTS: Increased risk association was observed for patients with at least one TRC in the upper aero digestive tract (UADT) for variations in SULT1A1 Arg²¹³His, mEH Tyr¹¹³His, hOGG1 Ser³²⁶Cys, XRCC1 Arg²⁸⁰His and BRCA2 Asn³⁷²His. Gene-environment interactions were assessed using MDR analysis. The overall best model by MDR was tobacco habit/p53(Arg/Arg)/XRCC1(Arg³⁹⁹His)/mEH(Tyr¹¹³His) that had highest Cross Validation Consistency (8.3) and test accuracy (0.69). This model also showed significant association using logistic regression analysis. CONCLUSION: This is the first Indian study on a multipathway based approach to study genetic susceptibility to cancer in tobacco associated MPN. This approach could assist in planning additional studies for comprehensive understanding of tobacco carcinogenesis

High-risk human papillomavirus (HPV) screening and detection in healthy patient saliva samples: a pilot study

<p>Abstract</p> <p>Background</p> <p>The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence.</p> <p>Methods</p> <p>Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity.</p> <p>Results</p> <p>Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (<it>p </it>< 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18.</p> <p>Conclusions</p> <p>The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.</p