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Review Article Open Access
Jyothi M. Narahari, Prajwal Guruswamy, Navyashree M. Jagadeesha, Kusuma K. Shivashakar, Divya P. Kumar, Prashanth S. Narayana, Prashant M. Vishwanath, Akila Prashant
Published online April 15, 2024
Gene Expression. doi:10.14218/GE.2023.00128
Abstract
Iron overload is a significant complication commonly observed in individuals with β-thalassemia, resulting from enhanced iron absorption due to ineffective erythropoiesis and frequent [...] Read more.

Iron overload is a significant complication commonly observed in individuals with β-thalassemia, resulting from enhanced iron absorption due to ineffective erythropoiesis and frequent blood transfusions. Iron overload can lead to severe tissue damage and organ dysfunction, significantly impacting the quality of life for those affected. Additionally, recent research indicates that iron overload may also adversely impact mitochondrial function, further exacerbating the pathophysiology of this disease. Excessive iron accumulation in mitochondria can impair the electron transport chain, reduce adenosine tri phosphate synthesis, and increase the generation of reactive oxygen species, resulting in elevated tissue damage and clinical complications. Emerging evidence suggests that specific mitochondrial DNA (mtDNA) mutations may further contribute to the severity of iron overload in β-thalassemia patients. Currently, the clinical management of iron overload in patients with β-thalassemia primarily relies on conventional iron chelation therapies, aiming to reduce iron burden and prevent tissue damage. However, cases involving mtDNA mutations introduce additional complexities, necessitating personalized treatment approaches. Advances in gene therapy and mitochondrial replacement strategies offer promising avenues for potential targeted interventions. This review provides a comprehensive overview of the mechanisms underlying iron overload in β-thalassemia and its association with mtDNA mutations. It discusses the clinical manifestations, diagnostic challenges, and current treatment options for managing iron overload, while also highlighting emerging research directions and potential therapeutic targets for improved patient care. Ultimately, a better understanding of the complex interplay between iron overload and mtDNA mutations in β-thalassemia will pave the way for innovative strategies to alleviate the disease burden.

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Original Article Open Access
Jinlin Hou, Qin Ning, Zhongping Duan, Yu Chen, Qing Xie, Lunli Zhang, Shanming Wu, Hong Tang, Jun Li, Feng Lin, Yongfeng Yang, Guozhong Gong, Yanwen Luo, Shelley Xie, Hongyuan Wang, Roberto Mateo, Tahmineh Yazdi, Frida Abramov, Leland J. Yee, John Flaherty, Chengwei Chen, Yan Huang, Mingxiang Zhang, Jidong Jia
Published online April 15, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00417
Abstract
After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to [...] Read more.

After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.

All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed.

The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: −1.5%, (95% CI: −6.4 to −3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, −2.85 mL/min vs. −3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.

The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

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Review Article Open Access
Nelson Rangel, Valentina Camargo, Giovanny Castellanos, Maribel Forero-Castro, Milena Rondón-Lagos
Published online April 10, 2024
Gene Expression. doi:10.14218/GE.2023.00154
Abstract
Breast cancer (BC) is the type of cancer with the highest incidence and mortality rates in women in the world. In the treatment of this neoplasia, several therapies are applied, [...] Read more.

Breast cancer (BC) is the type of cancer with the highest incidence and mortality rates in women in the world. In the treatment of this neoplasia, several therapies are applied, including radiotherapy, hormonal therapy, chemotherapy, and biological therapy. Although most patients respond to these types of therapy, some patients over time, develop resistance or eventually relapse. Considering the above, future therapeutic concepts in BC are being directed at individualization of therapy and escalation of treatment based on tumor biology through the use of gene therapy. In this regard, a new genomic engineering technology, called the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9), has acquired great importance in recent years, as a potential gene editing tool, extensively applied in human cancer research and cancer treatment. The aim of this review was to describe the advantages, limitations, and applications of CRISPR gene editing technology in BC treatment. Our review emphasizes the innovative facets and profound importance of CRISPR gene editing technology within the BC treatment landscape. Additionally, it provides valuable information to consider when evaluating the risks associated with the implementation of CRISPR-Cas9 technology in BC therapy.

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Original Article Open Access
Maryam Yousefi, Motahare-Sadat Hashemi, Maryam Peymani, Kamran Ghaedi, Shiva Irani, Masoud Etemadifar
Published online April 9, 2024
Gene Expression. doi:10.14218/GE.2023.00103
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder with unclear molecular mechanisms. Noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), [...] Read more.

Parkinson’s disease (PD) is a common neurodegenerative disorder with unclear molecular mechanisms. Noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been identified as critical regulators of gene expression. This study aimed to investigate the triple network of lncRNA-miRNA-mRNA, known as competing endogenous RNAs (ceRNAs), and to identify essential lncRNAs that regulate PD-related gene expression through their target miRNAs. The study also identified a common triple network between COVID-19 and PD that may contribute to exacerbating PD symptoms.

A bioinformatics approach was employed to construct a PD ceRNA network using common PD genes, miRNAs and lncRNAs with the highest interaction with their targets. Also, a PD-COVID-19 triple network was constructed by integrating PD network nodes into the COVID-19 network.

The PD ceRNA network comprised 34 nodes, including 12 lncRNAs, 16 miRNAs with interconnections and six mRNAs, some of which were related to COVID-19. The network showed parallel expression of the SNCA and PARK7 genes as well as the NEAT1 and MALAT1 lncRNAs in both PD and COVID-19.

This study provide insights into the molecular mechanisms underlying the worsening of symptoms in PD patients with COVID-19. The PD and COVID-19 ceRNA network indicates that coronavirus could worsen PD symptoms by altering the expression of some genes related to PD. Therefore, COVID-19 could dysregulate the common RNAs involved in PD through lncRNAs, miRNAs.

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Research Letter Open Access
Shalini Bansal, Tamar Taddei, Rebecca Wells, Marina Serper, Theresa Bittermann, Nadim Mahmud, David E. Kaplan
Published online April 8, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00554
Original Article Open Access
Haina Fan, Shujuan Lei, Zhimin Zhao, Yan Huang, Hui Wang, Xudong Liu, Xiaodong Li, Min Xu, Wei Zhang, Kewei Sun, Huichun Xing, Yang Mei, Jiaquan Huang, Chuanwu Zhu, Kejun Zhang, Yali Zong, Xizhong Shen, Qing Xie, Chenghai Liu
Published online March 27, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00521
Abstract
The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma (HCC) has not been established. [...] Read more.

The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma (HCC) has not been established. Here, we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu (FZHY) on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir (ETV).

A multicenter retrospective cohort study was performed. Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment. The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests. Propensity score matching was used for confounding factors. Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation.

Out of 910 chronic hepatitis B patients, 458 were in the ETV+FZHY group and 452 were in the ETV group. After propensity score matching, the 5-year cumulative incidence of HCC was 9.8% in the ETV+FZHY group and 21.8% in the ETV group (p<0.01). The adjusted hazard ratio for HCC was 0.216 (0.108, 0.432) when FZHY treatment was >36 months. Age, diabetes, alanine aminotransferase, γ-glutamyl transpeptidase, albumin, hepatitis B e-antigen, and fibrosis 4 score were associated with the occurrence of HCC. FZHY decreased the risk of HCC in patients aged >45 years with a hepatitis B virus DNA level of ≥2,000 IU/l.

Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV, possibly due to the antifibrotic properties of FZHY.

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Original Article Open Access
Timothy A. Skyring, Judy R. Mullan, Wade Wallace, Sosan Nasir, Kylie J. Mansfield
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00029
Abstract
Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment [...] Read more.

Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment on the background of a cancer where the potential for over-treatment and under-treatment is real. This study aimed to investigate the influence of cancer- and patient-related factors on the initial treatment decision for men with a new diagnosis of PCA and to evaluate treatment decisions against relevant guidelines.

This study undertook a retrospective audit of the clinical records of 545 men who were diagnosed with PCA at four Australian urology services. Age, comorbidities, and cancer-related factors were recorded, with patients divided into risk groups based on cancer factors.

Cancer risk stratification emerged as a primary determinant influencing individual treatment choices, with low-risk patients being more likely to have active surveillance and those classified as intermediate or high-risk being more likely to have TCI. Surgery was more commonly offered to younger patients and those with fewer comorbidities. While 80% of patients received guideline-concordant treatment, 20% were identified as being over-treated, receiving TCI despite limited life expectancy and/or high comorbidities.

Managing men diagnosed with PCA should avoid under-treatment in young, otherwise healthy individuals with aggressive cancer by offering TCI. Conversely, over-treatment (unnecessary treatment), especially in men with low-grade cancer or individuals with limited life expectancy due to significant comorbidities, should be avoided to prevent unnecessary treatment when competing causes are more likely to be fatal than prostate cancer.

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Review Article Open Access
Xi-Nuo Zhang, Sheng-Qiang Tong, Jiang-Jiang Qin, Xiao-Qing Guan
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00007
Abstract
Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, [...] Read more.

Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, sterols, and alkaloids. Huaier has been shown to demonstrate potent antitumor effects in a variety of cancer types, including breast cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, and others. In recent years, multiple in-vitro experiments have confirmed the good antitumor effect of Huaier and its mechanism of action, such as inhibiting proliferation, inducing apoptosis and oxidative stress, interfering with cell cycle arrest, inhibiting tumor metastasis and angiogenesis, inducing autophagy, and regulating immune function. In addition, multiple in-vivo studies and clinical trials have demonstrated the multidimensional antitumor potential of Huaier, such as slowing tumor progression, reversing drug resistance, improving chemotherapy drug sensitivity, and extending the survival time of cancer patients. In this article, the extraction methods of Huaier and its properties for the treatment of many cancers are reviewed. Moreover, the current molecular mechanisms of Huaier are summarized, revealing that it has great potential as an anticancer drug and providing strong theoretical support for related research. Furthermore, this review also provides suggestions for further research on the anticancer effects of Huaier, hoping to offer fresh perspectives for researchers in the realm of anticancer medicine.

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Review Article Open Access
Mohd Yusuf
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00041
Abstract
Cervical cancer is a significant public health concern worldwide. Current screening approaches include Pap smears, human papillomavirus testing, visual inspections, and emerging [...] Read more.

Cervical cancer is a significant public health concern worldwide. Current screening approaches include Pap smears, human papillomavirus testing, visual inspections, and emerging molecular techniques, aimed at enhancing precision and accessibility. The landscape also includes the increasing prominence of self-sampling and telemedicine, which broaden the reach of screening services. Human papillomavirus vaccination programs targeting young girls have the potential to significantly reduce long-term risk. These evolving strategies are supported by global initiatives such as the World Health Organization’s Cervical Cancer Elimination Initiative, aiming to increase screening efforts and reduce the global impact of cervical cancer. The key findings of this study suggested that current methodologies for the detection and prevention of cervical cancer are a little beneficial and there is a pressing need to use advanced technologies such as highly sophisticated equipment integrated with artificial intelligence. In addition, the detection of cervical cancer screening provides insights into evolving methodologies, promising prospects, and nuanced challenges that must be addressed to prevent this condition in females worldwide. Looking forward, future cervical cancer screening involves further refinements in molecular testing, expanded vaccine coverage, and the integration of telehealth solutions, promising increased accessibility and improved early detection to overcome insightful challenges.

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Review Article Open Access
Acharya Balkrishna, Nidhi Sharma, Deepika Srivastava, Ankita Kukreti, Stuti Srivastava, Vedpriya Arya
Published online March 25, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00086
Abstract
This review explores the convergence of traditional wisdom and modern science in the realm of herbal medicines, focusing on the safety, efficacy, and bioactivity of these natural [...] Read more.

This review explores the convergence of traditional wisdom and modern science in the realm of herbal medicines, focusing on the safety, efficacy, and bioactivity of these natural remedies in contemporary healthcare. The rich history of herbal medicines, deeply embedded in cultural traditions, is witnessing a resurgence as the quest for holistic and personalized healthcare gains momentum. Herbal medicine, a time-honored practice passed down through generations, is experiencing renewed interest amid the growing acknowledgment of its potential benefits. This review delves into the safety profiles of herbal remedies, subjecting them to rigorous scientific scrutiny. Additionally, it investigates the efficacy of herbal interventions, aiming to bridge the gap between historical anecdotes and empirical research. The complex bioactivity of herbal compounds, often containing numerous active ingredients, is a focal point, unraveling the mechanisms through which these natural substances interact with the human body. In a world where the synthesis of traditional wisdom and modern science holds promise for advancing healthcare, this review contributes to the ongoing dialogue. By critically examining the safety, efficacy, and bioactivity of herbal remedies, it aims to illuminate the evolving landscape of herbal medicine. The goal is to integrate the best of both worlds to enhance global well-being, acknowledging the potential of herbal medicine as a valuable complement to modern healthcare practices.

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Review Article Open Access
Zahra Shafieizadeh, Zohreh Shafieizadeh, Maryam Davoudi, Reza Afrisham, Xiaolei Miao
Published online March 25, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00397
Abstract
Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver [...] Read more.

Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver regeneration. Nevertheless, residual microtumors may also exploit these pathways to reappear and metastasize. Therapeutically targeting molecules that are differentially regulated between normal cells and malignancies, such as fibrinogen-like protein 1 (FGL1), appears to be an effective approach. The potential functions of FGL1 in both regenerative and malignant cells are discussed within the ambit of this review. While FGL1 is normally elevated in regenerative hepatocytes, it is normally downregulated in malignant cells. Hepatectomy does indeed upregulate FGL1 by increasing the release of transcription factors that promote FGL1, including HNF-1α and STAT3, and inflammatory effectors, such as TGF-β and IL6. This, in turn, stimulates certain proliferative pathways, including EGFR/Src/ERK. Hepatectomy alters the phase transition of highly differentiated hepatocytes from G0 to G1, thereby transforming susceptible cells into cancerous ones. Activation of the PI3K/Akt/mTOR pathway by FGL1 allele loss on chromosome 8, a tumor suppressor area, may also cause hepatocellular carcinoma. Interestingly, FGL1 is specifically expressed in the liver via HNF-1α histone acetylase activity, which triggers lipid metabolic reprogramming in malignancies. FGL1 might also be involved in other carcinogenesis processes such as hypoxia, epithelial-mesenchymal transition, immunosuppression, and sorafenib-mediated drug resistance. This study highlights a research gap in these disciplines and the necessity for additional research on FGL1 function in the described processes.

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Case Report Open Access
Taha Khalid, Gavin Calpin, Alina Ahmed, Ala Yousif
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00002
Abstract
Cancer treatment has been revolutionized in the last 10 years. Previously, highly toxic chemotherapy regimens that attack both healthy cells and cancer cells as well as induce significant [...] Read more.

Cancer treatment has been revolutionized in the last 10 years. Previously, highly toxic chemotherapy regimens that attack both healthy cells and cancer cells as well as induce significant side effects were used. Nowadays, a more targeted approach is employed. Cancer cells are being treated at the molecular level. Patients with carcinoma of unknown primary who previously only had “broad spectrum” combination therapy as a treatment option can now have their cancer’s genome sequenced with next-generation sequencing in a matter of hours and be offered a more targeted approach. Here, we report a case of a patient with metastatic cancer of an unknown primary origin who was progressing on multiple lines of treatment. Next-generation sequencing showed that the patient had a high tumor mutational burden; therefore, he was able to access immunotherapy through a compassionate access scheme, which resulted in a near complete and sustained clinical and radiological response.

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Original Article Open Access
Xukuo Liu, Jiangping Zhan, Xiaohui Zhao, Huanfang Fan, Lijun Zhao, Min Li, Wenli Yu, Dehui Li
Published online March 25, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00041
Abstract
With the highest incidence rate and death rate among malignant tumors, lung cancer is the most prevalent malignant tumor worldwide. Tumor-node-metastasis (TNM) staging provides [...] Read more.

With the highest incidence rate and death rate among malignant tumors, lung cancer is the most prevalent malignant tumor worldwide. Tumor-node-metastasis (TNM) staging provides a basis for clinical therapy and prognosis while the fundamental principle of traditional Chinese medicine (TCM) is the syndrome differentiation and treatment. This study offers an objective foundation for the distinction and classification of TCM syndromes by methodically assessing the relationship between TNM staging indicators and the various types of the syndrome in lung cancer.

To find pertinent material, we searched a number of databases, including CNKI, PubMed, VIP, and Wanfang. Literature on the relationship between TCM syndrome categories and TNM staging indexes of lung cancer published from the database’s inception until May 2023 was gathered. The meta-analysis was carried out using Rev Man 5.4.

In the end, seven pieces of literature totaling 264 patients were included. Lung cancer is mainly characterized by phlegm dampness syndrome, Qi Yin deficiency syndrome, Yin deficiency internal heat syndrome, and Qi stagnation and blood stasis syndrome. In stage I and II, phlegm dampness syndrome > Yin deficiency internal heat syndrome (p < 0.5), phlegm dampness syndrome > Qi Yin deficiency syndrome (p < 0.5), phlegm dampness syndrome > Qi stagnation and blood stasis syndrome (p < 0.5). In stages III and IV, Qi Yin deficiency syndrome > Qi stagnation and blood stasis syndrome > Yin deficiency internal heat syndrome > phlegm dampness syndrome (p < 0.5).

Phlegm dampness syndrome is the main syndrome in stages I and II of lung cancer, while Qi and Yin deficiency syndromes are the main syndromes in stages III and IV of lung cancer.

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Case Report Open Access
Gengbiao Zhang, Lingmei Kong, Bixia Wu, Xuewen Wang, Jin Wang, Yian Chen, Xinhui Su, Jinghua Wu, Wenbin Zheng
Published online March 25, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00090
Abstract
Impairment in the cerebral glymphatic system may be one of the primary etiologic reasons for insomnia. Traditional Chinese medicine (TCM) physiotherapy is helpful for treating insomnia [...] Read more.

Impairment in the cerebral glymphatic system may be one of the primary etiologic reasons for insomnia. Traditional Chinese medicine (TCM) physiotherapy is helpful for treating insomnia patients, with few side effects; however, its influence on glymphatic system function has not yet been examined. The DTI-ALPS (diffusion tensor image analysis along the perivascular space) technique and structural brain network graph theory analysis are the only current methods that can show the glymphatic system’s function and the operating efficiency of the neurofibrillary network in a noninvasive and quantitative manner, but their utility has yet to be proven. We employed DTI-ALPS and structural brain network small-worldness to examine changes in the glymphatic system’s function and the network’s working efficiency before and after TCM meridian sinew treatment in a 35-year-old female with chronic insomnia. The ALPS index and small-worldness, the Insomnia Severity Index, and the Pittsburgh Sleep Quality Index were collected at various time intervals following therapy. The results showed that the patient’s glymphatic system functioning, neurofibrillary network arrangement status, and insomnia symptoms improved during the therapy period. Additionally, her glymphatic system functioning and network status had stabilized and her quality of sleep had improved one month after the treatment ended. Thus, TCM physiotherapy can improve insomnia symptoms, and this report suggests that the corresponding mechanism of action may be achieved by repairing the glymphatic system’s function and optimizing the state of neurofibrillary network arrangement, providing a new perspective for the study of the TCM therapeutic mechanism of insomnia.

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Original Article Open Access
Aibing Rao
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00034
Abstract
About 30% of lung cancer patients are accessible to targeted therapy or immunotherapy based on the current criteria. In this study, a novel gene cluster expression analysis was [...] Read more.

About 30% of lung cancer patients are accessible to targeted therapy or immunotherapy based on the current criteria. In this study, a novel gene cluster expression analysis was introduced with a goal to potentially expand the treatments to more patients based on the proposed criteria.

Selected gene expression omnibus data sets were downloaded, normalized, and analyzed. A univariate recurrence prediction model was built based on the receiver operating characteristic, for which an optimal cutoff was determined to set abnormality status, called the gene cluster expression index (GCEI). Recurrence and survival risks were calculated and compared between two subgroups indexed by the GCEI. Moreover, a combinatory GCEI was also introduced and its performance was analyzed for combined multiple cluster statuses.

The recurrence risks of the patient subgroups with abnormally expressed clusters with GCEI = 1 were much higher than for the corresponding normal subgroup with GCEI = 0. The higher risks ranged from 120–300% that of the corresponding lower-risk group.

The GCEI can be used to classify lung cancers with dramatically different recurrence risks and may be used to guide targeted therapy or immunotherapy for patients who are in a high-risk group but do not qualify for such treatment according to conventional companion tests.

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Original Article Open Access
Nerses Berberian, Hayk Sargsyan, Lilit Sahakyan, Ani Gagik Ghabuzyan, Haykuhi Geokchyan-Kzhdryan, Sevana Abnoosi, Arby Leonian, Katarina Dalunde Eriksson, Axel Gräwingholt
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00034S
Abstract
Breast cancer is one of the greatest global health concerns for women, with rising incidence rates and mortality projections, while affordability and access to mammography screening [...] Read more.

Breast cancer is one of the greatest global health concerns for women, with rising incidence rates and mortality projections, while affordability and access to mammography screening and diagnosis, especially in low- and middle-income countries, remain a challenge. This retrospective clinical validation study evaluated a breast cancer pre-screening solution (BCPS) based on a commercially available smartphone with a thermal imaging sensor powered by artificial intelligence. The purpose was to measure the performance of the BCPS tool compared to mammography, the gold standard for first-pass examination in breast cancer screening.

The evaluation was conducted in the Erebouni Medical Center Breast Unit in Armenia over a period of six months. We tested a cohort of 478 women of whom 45 were finally diagnosed with breast cancer after biopsy. Participants were first screened with the BCPS before undergoing the standard breast screening pathway. After studying the mammography results, if malignancy was discovered, a biopsy was performed and taken as the ground truth when comparing with BCPS artificial intelligence results.

When combined with patient-reported or clinical symptoms, the BCPS tool achieved a sensitivity of 89% and a specificity of 83% compared to mammography. When clinical or patient-reported symptoms were not taken into account, sensitivity was considerably lower (60%), while specificity was higher (88.2%).

The BCPS tool, in combination with basic clinical exams and patient-reported symptoms, may serve as a robust triaging tool for breast cancer detection where mammography is not available or affordable, identifying the majority of women who need further diagnostic assessment.

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Original Article Open Access
Xin Ji, Hong Chen
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00002
Abstract
Currently, the mechanism of occurrence and development of colonic polyps and colonic cancer has not been fully elucidated. Previous studies have shown a certain relationship between [...] Read more.

Currently, the mechanism of occurrence and development of colonic polyps and colonic cancer has not been fully elucidated. Previous studies have shown a certain relationship between bile acid (BA) profile and the development of colonic cancer. Through an analysis of the relationship between alterations in the serum BA profile and colonic neoplasms, this study sought to develop new biomarkers for assessing the risk of colon illnesses and offer fresh perspectives for identifying treatment targets.

The study encompassed 135 individuals who showed no abnormalities during colonoscopy, 204 patients with colonic polyps, and 92 patients with colonic cancer, all diagnosed and treated at Zhongda Hospital, Southeast University, from January 1, 2022, to June 1, 2023. Serum BA profiles, liver function, and clinical data were collected for statistical analysis.

The concentration of deoxycholic acid in patients with colonic neoplasms was lower than that in the control group, whereas levels of taurocholic acid, taurochenodeoxycholic acid, and glycochenodeoxycholic acid were significantly higher in the colonic neoplasms group than in the control group (P < 0.05). Subgroup analysis revealed that there were statistical differences in the content of cholic acid, ursodeoxycholic acid, and glycoursodeoxycholic acid among different pathological types of colonic neoplasms. Logistic regression analysis indicated a negative correlation between the concentration of glycodeoxycholic acid and the risk of developing colonic neoplasms.

Compared with the normal population, the serum BA profile of colonic neoplasms patients has changed. Patients with colonic neoplasms exhibit elevated levels of primary conjugated BAs and decreased levels of secondary free BA (deoxycholic acid).

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Original Article Open Access
Emmanuel Sánchez, Alba Verdú, Arancha Carbonell, Juan Luis Alcazar
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2023.00034
Abstract
Three-dimensional power Doppler (3DPD) ultrasound has been used for assessing adnexal masses, and in this study, we aimed to perform a meta-analysis to evaluate its role in the [...] Read more.

Three-dimensional power Doppler (3DPD) ultrasound has been used for assessing adnexal masses, and in this study, we aimed to perform a meta-analysis to evaluate its role in the differential diagnosis of adnexal masses.

A search for primary studies assessing the diagnostic performance of 3DPD in discriminating benign from malignant masses carried out between January 1990 and May 2023 was performed in Medline (PubMed), Scopus, and Web of Science databases with study quality evaluated using QUADAS-2.

We identified 404 citations. Ultimately, 18 studies comprising 2,975 women were included, and the mean prevalence of malignant lesions was 37%. In most cases, the quality of studies was moderate. Overall, pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including any type of mass were 77% (95% confidence interval [CI] = 52%–91%), 80% (95% CI = 37%–97%), 3.9 (95% CI = 0.7–20.9), and 0.29 (95% CI = 0.10–0.81), respectively. Heterogeneity was high for both sensitivity and specificity. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including only “complex” or “suspicious” adnexal masses were 90% (95% CI = 82%–94%), 88% (95% CI = 74%–95%), 7.3 (95% CI = 3.2–16.4), and 0.12 (95% CI = 0.06–0.22), respectively. Heterogeneity was moderate for both sensitivity and specificity. We could not perform quantitative synthesis for studies estimating 3D vascular indexes.

The diagnostic performance of 3DPD for discriminating benign from malignant adnexal masses is good, and there is great heterogeneity in diagnostic criteria when using this technique.

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Original Article Open Access
Huimin Yin, Shouhua Zhang, Haixia Zhou, Changmi Deng, Yizhen Wang, Hongting Lu, Shaohua He, Ruixi Hua, Chunlei Zhou
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00006
Abstract
Wilms tumor is the most common renal malignancy in children. miR-146a, a highly conserved small noncoding RNA, plays a critical role in various human diseases. Increasing studies [...] Read more.

Wilms tumor is the most common renal malignancy in children. miR-146a, a highly conserved small noncoding RNA, plays a critical role in various human diseases. Increasing studies have suggested that rs2910164 C>G polymorphism in miR-146a is associated with susceptibility to cancers. However, miR-146a rs2910164 C>G polymorphism influence on Wilms tumor remains unknown. The aim of this study was to evaluate the relationship between miR-146a rs2910164 C>G polymorphism and Wilms tumor susceptibility in Chinese children.

In the six-center case-control study, we enrolled 1,352 subjects from East China (416 cases and 936 healthy controls). The TaqMan method was adopted to genotype the miR-146a rs2910164 C>G polymorphism. Logistic regression models were utilized to assess the correlation between this polymorphism and the risk of Wilms tumor.

No significant association was observed between miR-146a rs2910164 C>G polymorphism and the susceptibility to Wilms tumor. Further stratification analysis also did not detect a significant relationship.

The present study showed no association of miR-146a rs2910164 C>G polymorphism with the risk of Wilms tumor in the Eastern Chinese population. Subsequent studies with a larger sample size will be required to validate these results.

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Original Article Open Access
Ashrafun Nessa, Shirin Akter Begum, Saif Ullah Munshi, Ferdousy Begum, Afroza Chowdhury, Noor-E-Ferdous
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00033
Abstract
The government of Bangladesh adopted visual inspection of the cervix with acetic acid method for cervical cancer screening in the majority of the district and sub-district hospitals. [...] Read more.

The government of Bangladesh adopted visual inspection of the cervix with acetic acid method for cervical cancer screening in the majority of the district and sub-district hospitals. Before alternative screening methods are adopted, the prevalence of high-risk human papillomavirus (HPV) genotypes among various geographical regions must be determined. Therefore, we aimed to determine the prevalence of high-risk HPV genotypes in urban and rural areas of Bangladesh.

This cross-sectional study was carried out at Bangabandhu Sheikh Mujib Medical University, Dhaka from July 2021 to June 2022. Using a multistage sampling method, cervical samples (N = 3,856) were collected from women aged 30–49 years attending visual inspection of the cervix with acetic acid at 16 centers (eight districts and eight sub-districts). HPV tests were performed by real-time PCR amplification. Descriptive analysis and Chi-square test/Fisher’s exact test were performed for associations, and a P value <0.05 was considered significant.

Among the 3,856 women, the overall prevalence of high-risk HPV was 3.6%, with 49 (1.3%) women testing positive for HPV16, 12 (0.3%) women testing positive for HPV18, and 65 (1.7%) testing positive for other high-risk HPV genotypes. There was a significant variation in the prevalence of high-risk HPV among the divisions (P = 0.001), with the highest infection rate (7.1%) observed among women in rural Sylhet and the lowest in rural Mymensingh (0.5%). No significant difference in high-risk HPV prevalence was found between the urban and rural women, except in Mymensingh.

The low prevalence of high-risk HPV (3.6%) among Bangladeshi women with regional variation should be considered by policymakers during the development of cervical cancer prevention policies.

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