Increased Survival Rate Research Articles

Therapeutic targeting at genome mutations of liver cancer by the insertion of HSV1 thymidine kinase through Cas9-mediated editing.

Liver cancer is one of the most lethal malignancies for humans. The treatment options for advanced-stage liver cancer remain limited. A new treatment is urgently needed to reduce the mortality of the disease. In this report, we developed a technology for mutation site insertion of a suicide gene (herpes simplex virus type 1- thymidine kinase) based on type II CRISPR RNA-guided endonuclease Cas9-mediated genome editing to treat liver cancers. We applied the strategy to 3 different mutations: S45P mutation of catenin beta 1, chromosome breakpoint of solute carrier family 45 member 2-alpha-methylacyl-CoA racemase gene fusion, and V235G mutation of SAFB-like transcription modulator. The results showed that the herpes simplex virus type 1-thymidine kinase insertion rate at the S45P mutation site of catenin beta 1 reached 77.8%, while the insertion rates at the breakpoint of solute carrier family 45 member 2 - alpha-methylacyl-CoA racemase gene fusion were 95.1%-98.7%, and the insertion at V235G of SAFB-like transcription modulator was 51.4%. When these targeting reagents were applied to treat mouse spontaneous liver cancer induced by catenin beta 1S45P or solute carrier family 45 member 2-alpha-methylacyl-CoA racemase, the mice experienced reduced tumor burden and increased survival rate. Similar results were also obtained for the xenografted liver cancer model: Significant reduction of tumor volume, reduction of metastasis rate, and improved survival were found in mice treated with the targeting reagent, in comparison with the control-treated groups. Our studies suggested that mutation targeting may hold promise as a versatile and effective approach to treating liver cancers.

TLR7 Agonist-Loaded Gadolinium Oxide Nanotubes Promote Anti-Tumor Immunity by Activation of Innate and Adaptive Immune Responses.

Improving the delivery of biomolecules to DCs and lymph nodes is critical to increasing their anti-tumor efficacy, reducing their off-target side effects, and improving their safety. In this study, Gd2O3 nanotubes with lengths of 70-80 nm, diameters of 20-30 nm, and pore sizes of up to 18 nm were synthesized using a facile one-pot solvothermal method. The Gd2O3 nanotubes showed good adsorption capacity of OVA and TLR7a, with a loading efficiency of about 100%. The Gd2O3 nanotubes showed pH-sensitive degradation and biomolecule release properties; the release of gadolinium ions, OVA, and TLR7a was slow at pH 7.4 and fast at pH 5. The Gd2O3 nanotubes showed 2.6-6.0 times higher payload retention around the injection site, 3.1 times higher cellular uptake, 1.7 times higher IL1β secretion, 1.4 times higher TNFα secretion by BMDCs, and markedly enhanced draining lymph node delivery properties. The combination of OVA, TLR7a, and Gd2O3 nanotubes significantly inhibited tumor growth and increased survival rate compared with only OVA-TLR7a, only OVA, and saline. The Gd2O3 nanotubes are biocompatible and can also be used as radiation sensitizers.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study

BackgroundWith the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth...

The role of ultrasound in the management of carotid artery disease after head and neck radiotherapy treatment

AbstractHead and neck cancers (HNC) are a significant cause of morbidity and mortality globally. Radiotherapy (RT) is used heavily in the treatment of HNCs and has undergone rapid development since the 1980s which has led to increased survival rates in this patient group. Carotid artery stenosis and an increased incidence of stroke and transient ischaemic attack (TIA) have all been repeatedly described as a side effect of head and neck RT with vascular fibrosis implicated in its pathogenesis. The appearance of RT induced carotid stenosis displays a different phenotype to typical atherosclerotic plaque which can be appreciated both in histology samples and on ultrasound imaging. Ultrasound may also have a role to play in screening HNC patients who undergo RT to identify those at risk of suffering cerebrovascular events.

Effects of transition programmes to adulthood for adolescents and young adults with CHD: a systematic review with meta-analysis.

The increased survival rate among individuals with CHD has sparked interest in their transition to adult healthcare. Although there is a general agreement on the importance of transition interventions, the empirical evidence supporting them is insufficient. Therefore, this study aimed to conduct a systematic review and meta-analysis of transition interventions for adult healthcare in adolescents and young adults. A literature search was conducted for studies comparing the quantitative effects of transition interventions with control groups, published up to March 15, 2023, in major databases (CENTRAL, Embase, PubMed, Web of Science, CINAHL, KISS, and KMbase), major clinical trial registries, academic journal sites related to the topic, and grey literature databases. Ten studies involving a total of 1,297 participants were identified. Transition interventions proved effective in enhancing disease-related knowledge (Hedge's g = 0.89, 95% CI = 0.29-1.48) and self-management (Hedge's g = 0.67, 95% CI = 0.38-0.95), as well as reducing loss to follow-up (OR = 0.41, 95% CI = 0.22-0.77). The certainty of evidence for the estimated values of each major outcome was low or very low. This study supports the implementation of transition interventions by demonstrating that they can improve patients' disease knowledge and self-management, while also promoting treatment continuity. However, since the available data on transition interventions for adolescents and young adults with CHD remain limited, the widespread adoption of structured transition interventions in the future may alter the conclusions of this study. URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42023399026.

Magnolol attenuates macrophage pyroptosis triggered by Streptococcus equi subsp. zooepidemicus

Streptococcus equi subsp. zooepidemicus (SEZ) is a zoonotic bacterial pathogen that causes life-threatening infections and various diseases such as meningitis, endocarditis and pneumonia. With the use of antibiotics being severely restricted in the international community, an alternative to antibiotics is urgently needed against bacterial. In the present study, the herbal extract magnolol protected mice against SEZ infection, reflected by increased survival rate and reduced bacterial burden. A pro-inflammatory form of cell death occurred in SEZ-infected macrophage. Magnolol downregulated the expression of pyroptosis-related proteins and reduced the formation of cell membrane pores in infected macrophages to suppress the development of subsequent inflammation. We further demonstrated that magnolol directly suppressed SEZ-induced macrophage pyroptosis, which partially protected macrophages from SEZ infection. Our study revealed that magnolol suppressed inflammation and protected mice against SEZ infection, providing a possible treatment for SEZ infection.

Abstract 2447: Identification of tumor marker gangliosides for early cancer detection: A mass spectrometry approach

Abstract Tumor-marker gangliosides (TMGs) have enormous potential for early-stage cancer detection as diagnostic biomarkers despite being relatively understudied in this context. AOA Dx is focused on the development of a mass spectrometry platform for the quantitation of TMGs in human serum, particularly disialogangliosides GD2 and GD3. The development of a mass spectrometry platform for TMG quantitation may allow for the identification of diagnostic signatures for early-stage cancer detection. Briefly, we monitored fragment moieties characteristic of gangliosides in an untargeted fashion by mass spectrometry. We then identified those differentially altered in cancerous groups compared to normal, and subsequently performed targeted MRM analysis. Through these investigations, we have identified multiple TMGs, specifically multiple types of GD2 and GD3 species characterized by unique lipid tails across different cancer types in human serum from confirmed cancer diagnoses. Other ganglioside classes including GMs and relatively understudied GTs were also identified in this study. Notably, the serum of melanoma and ovarian cancer patients exhibited significantly increased levels of several ganglioside species compared to age-matched healthy serum, highlighting the potential of TMGs as a promising avenue for cancer diagnosis. Further experiments will focus on refining this mass spectrometry method and expand demographic representation to confirm our initial findings and identify additional TMGs of interest. In addition, we intend to apply immune-based platforms such as thin-layer chromatography and ELISA, which have already shown promising results in the detection and quantitation of these compounds. Taken together, AOA Dx is advancing the development of a high-throughput mass spectrometry platform designed for the detection of TMGs, with a primary focus on GD2 and GD3. Our objective is the identification of a diagnostic disease signature for early-stage cancer detection. The validation of this type of diagnostic panel would allow for expedited diagnosis and treatment of cancers currently diagnosed at late stages, ultimately reducing healthcare costs and increasing survival rates. Future research will aim to validate these biomarkers in independent prospective studies. Citation Format: Rachel Culp-Hill, Collin Hill, Adele Blackler, William Ricketts. Identification of tumor marker gangliosides for early cancer detection: A mass spectrometry approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2447.

Abstract 1268: Immune activation characterization via amino acid concentration signatures for multi-cancer early detection and CDKi treatment response prediction

Abstract Early detection of cancer can increase survival rates by 5-10 times. In the US, a significant portion of cancers are still detected at a late stage, for example, 32.1% of breast cancer, 45.5% of lung cancer, 22.8% of colon cancer patients were diagnosed at advanced stage. Early detection is challenging because many cancers are asymptomatic in early stages, although cancer screening can detect cancer before symptoms emerge. Current standard-of-care screening programs are limited and directed to single types of cancer. Non-invasive multi-cancer early detection (MCED) is urgently needed because it can screen for several cancer types with a single blood test, increasing cancer screening coverage while avoiding cumulative false positive rates. Developmental MCED approaches usually rely on detection of circulating tumor DNA (ctDNA) released from tumors. However, ctDNA signals scale with tumor burden limiting sensitivity and specificity, particularly for early-stage cancers, while also limiting applicability to precision oncology. Here we report a MCED approach with superior sensitivity and specificity, which can also be used to predict treatment response. We introduce a novel strategy for detecting cancers from blood plasma, profiling the immune response to disease development rather than relying on detection of emerging diseased tissue. The platform is designed to detect alterations in the ratio of immunoglobulins and albumin, as well as class-switching among immunoglobulins, by measuring the overall concentration of amino acid residues incorporated into proteins in patient plasma. By using our biorthogonal chemistry labeling tool, we were able to measure and characterize amino acid concentration signatures (AACS) within the neat blood samples, including cysteine, free cysteine, lysine, tryptophan and tyrosine, which allowed us to observe distinct signatures for varying cancers including breast, prostate, colorectal and pancreatic cancers. We could identify 84% of cancers with <0.5% false positive rate (N=93). In this study, cancer AACS signatures were distinct from signatures measured with non-cancerous immune activation, including autoimmune diseases and infection. Moreover, AACS was also correlated to clinical features, such as cancer metastatic statuses and therapy response. With Cyclin-dependent Kinase 4/6 Inhibitors-treated advanced breast cancer patients as an example, we achieved 100% correct prediction of responding patients and 91.7% accurate predictions of non-responding patients by using AACS in treatment-naïve samples. Altogether, the novel AACS approach is a powerful combination of bioorthogonal chemistry and machine learning analysis in clinical practice, and it can be potentially used for cancer screening and support clinical decisions for treatment selection and patient stratification in new indications. Citation Format: Cong Tang, Patrícia Corredeira, Sandra Casimiro, Wesley Sukdao, Luís Costa, Emma Yates, Gonçalo Bernardes. Immune activation characterization via amino acid concentration signatures for multi-cancer early detection and CDKi treatment response prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1268.

Abstract 4845: Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity

Abstract Introduction: In recent years, immune checkpoint inhibitors (ICI) have revolutionized the landscape of treatment across a variety of cancers. Potential concerns regarding racial disparities in ICI access and therapeutic efficacy have been well documented. Recent studies have indicated improved ICI access and response outcomes in White patients compared to minority groups with head and neck cancer (HNC) and melanoma patients. In contrast, patients diagnosed with lung cancer have been mixed, with some research suggesting black patients may fare better with ICI therapy. Existing literature is largely limited to retrospective studies with small population sizes, and lacks comparisons of racial disparities across malignancies. We aim to describe and compare racial inequities in ICI outcomes in HNC, melanoma, and lung cancer. Methods: The TriNetX US Collaborative Network database was queried for patients >18 years-old with a diagnosis of head and neck cancer, melanoma or lung cancer that were treated with ICIs. Malignancy cohorts were defined by race: non-Hispanic White (NHW) and Black. Race cohorts were 1:1 propensity score matched (PSM) for comorbidities, oncologic stage, and chemoradiation treatment. Demographic differences in cohorts were evaluated prior to matching. Following PSM, overall survival and rates of autoimmunity were assessed at 5 years. Results: 19,443 NHW and 2,827 Black patients treated with ICI were identified. At a baseline, the Black patient cohorts had significantly higher rates of comorbidies (p<0.02). Across all malignancies, the geographic distribution of NHW patients was more equally distributed compared to Black patients (majority south). With PSM, black HNC patients had significantly lower survival rates compared to NHW [HR: 1.4 (1.2, 1.6), p=0.0002]. In melanoma, the same trend was present, though not significant [HR: 1.3 (0.95, 1.7), p=0.1]. In contrast, in lung cancer, Black patients had significantly higher survival rates compared to NHW patients [HR 0.78 (0.70, 0.86), p<0.0001]. In HN and lung cancer, NHW patients had significantly higher rates of autoimmune conditions after ICI therapy compared to Black [OR: 2.0 (1.4,2.8), 1.2 (1.0, 1.4), respectively]. Conclusion: This study represents the most extensive analysis of racial disparities on ICI outcomes across malignancies. This study found that black patients treated with ICIs had decreased survival rates at 5 years compared to NHW patients in HNC and melanoma, but increased survival rate in lung cancer. This disparity persisted following PSM, matching cohorts for comorbidities, oncologic stage and adjuvant therapy. Black patients also had significantly lower rates of autoimmunity in HN and lung cancer. Noted differences in survival may be a reflection of geographic practice differences, access to care and/or socioeconomic status. Further investigation is required to elucidate the underlying etiologies of these trends. Citation Format: Kathryn L. Nunes, Pablo Llerena, Praneet Kaki, Shreya Mandloi, Annie Moroco, Eric Mastrolonardo, David M. Cognetti, Adam J. Luginbuhl, Joseph M. Curry. Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4845.

Abstract 3346: JMJD6 as a novel tumorigenic factor and therapeutic target in group 3 (MYC-driven) medulloblastoma

Abstract Medulloblastoma (MB) is the most common type of childhood brain cancer worldwide. Although current treatment with surgery and extensive chemoradiation has led to increased survival rates, many MB patients still die from the disease. Moreover, surviving patients suffer severe long-term side effects as a consequence of treatment. It is therefore crucial to develop more effective and less toxic therapies. The most aggressive subtype of MB tumors often exhibits amplification or overexpression of the MYC oncogene. Patients with MYC-amplified MB exhibit a high frequency of cerebrospinal tumor dissemination, often experience treatment resistance and have extremely poor prognoses. While the MYC oncogene is established as the oncogenic driver in Group 3 MB, it has remained undruggable. Thus, targeting regulatory components of MYC and the signaling pathways regulated by it is of great potential therapeutic value. Studies have revealed that MB has very few germline mutations in cancer predisposition genes, suggesting that dysregulated epigenetic pathways might be critical in MB pathogenesis. Particularly, dysregulation of epigenetic modifiers, including histone methyltransferases and histone demethylases, is very common in Group 3 MB, compared to other MB subgroups. Therefore, it is important to identify such epigenetic modifiers that may have controls on MYC and its tumorigenic activities and explore these as the epigenetic drug-candidate targets in Group 3 (MYC-driven) MB. In this regard, we found that protein arginine demethylase Jumonji C domain-containing protein 6 (JMJD6), an emerging key epigenetic enzyme in cancers, is a novel regulator of MYC expression in MYC-driven MB. We observed high levels of JMJD6 that not only mirror MYC expression in the most aggressive MB but also correlate with poor outcomes in these patients. Knockdown of JMJD6 decreased MYC expression, cellular proliferation/survival and stemness in MYC-amplified MB cells. Mechanistically, our results revealed that JMJD6 forms complexes with proteins involved in maintaining and regulating the promoter-pause at super-enhancers, suggesting that JMJD6 can regulate MYC at the transcription level. Moreover, our in vivo analyses of JMJD6 inhibition, either with inducible gene knockdown or a pharmacologic small molecule inhibitor, demonstrated anti-MB potential with suppressed MYC expression. Based on this background and preliminary observations, we hypothesize that JMJD6 plays crucial roles in the most aggressive MB by regulating MYC expression and hence MYC-driven tumorigenesis. Accordingly, we hypothesize that targeting the JMJD6-MYC axis by JMJD6 inhibition can serve as a powerful therapeutic strategy for MYC-driven MB. Citation Format: Matthew Kling, Devendra Kumar, Sutapa Ray, Shantaram Joshi, Don Coulter, Nagendra K. Chaturvedi. JMJD6 as a novel tumorigenic factor and therapeutic target in group 3 (MYC-driven) medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3346.

Abstract 2317: Development and validation of a colorectal cancer prediction model: A nationwide cohort-based study

Abstract Background: Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and is a major cause of cancer-related mortality. Early diagnosis is critical to increase survival rates. While CRC screening has shown significant benefit, adherence remains low, and there is a need for better tools to identify high-risk patients. Risk prediction models were demonstrated to identify such patients. Aim: To establish an individualized risk prediction model for CRC diagnosis based on Electronic Health Records (EHR). Methods: This is a retrospective cohort study utilizing EHR data of Clalit Health Services (CHS) members aged 50-74 that were eligible for CRC screening, from January 2013 to January 2019. The model was trained to predict CRC diagnosis within two years using approximately 20,000 EHR features including socio-demographic information, laboratory results and medical history. Model performance, as a complementary screening method, was evaluated. Results: The study included 2679 subjects with CRC diagnosis and 1,133,713 subjects without CRC diagnosis. The model was trained on subjects from 2013-2017, and performance was validated on subjects from 2019 and a cohort of subjects that underwent fecal occult blood test (FOBT). Incidence values of CRC among subjects in the top 1% risk scores were higher than baseline (2.3% vs. 0.3%; lift 8.38; P-value <0.001). Characteristics of subjects by risk scores percentiles are presented in Table 1. Cumulative event probabilities increased with higher model scores, indicating a correlation between predicted and actual risk of CRC diagnosis. Model-based risk stratification among subjects with a positive FOBT, identified subjects with more than twice the risk for CRC compared to FOBT alone. Conclusions: We developed an individualized risk prediction model for CRC that can be utilized as a complementary decision support tool for healthcare providers to precisely identify patients at high risk for CRC and refer them to confirmatory testing. Citation Format: Samah Hayek. Development and validation of a colorectal cancer prediction model: A nationwide cohort-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2317.

Abstract 2137: Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis

Abstract Background: While high-resolution imaging and advancements in therapies have significantly improved breast cancer survival rates, 43,170 breast cancer patients will die in the United States in 2023 alone. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. Persistent cancer racial disparities remain due to a variety of risk factors. The SEER/CDC data show an 8% lower breast cancer incidence rate and a 41% higher mortality rate in Black/AA patients compared to their white counterparts. Methods: Chart review was conducted using Sentara MD Office/EPIC and VOA iKnowMedicine portals to update tumor relapse, metastasis, and survival in 577 TNBC patients. Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR/K-RAS/SIAH pathway activation is a major driving force of TNBC malignancy, racial disparity, early relapse, and high mortality. We propose to integrate SIAH expression to augment the existing clinicopathological parameters to improve patient risk stratification, therapy quantification, and relapse/survival prediction at the 1st-line neoadjuvant settings. Results: We report that cancer disparity and high mortality rates are even more pronounced in our racially-diverse communities in Hampton Roads Virginia. We discovered that SIAH is a tumor-specific, therapy-responsive, and prognostic biomarker in TNBC. High SIAH expression in residual tumors reflects tumor-driving EGFR/K-RAS/SIAH pathway activation (ON) that will predict cancer disparity, treatment resistance, early relapse, and poor survival. Low SIAH expression in residual tumors reflect EGFR/K-RAS/SIAH pathway inactivation (OFF) that will predict tumor remission and prolonged survival. Conclusion: We detect a major racial disparity of TNBC patients at Sentara-EVMS-VOA. Our local Black/AA TNBC patients have a 1.6-fold higher mortality rate than their White counterparts. Encouraged by our preliminary data, we aim to develop a SIAH-centered biomarker panel by measuring the EGFR/K-RAS/SIAH pathway activation (ON)/inactivation (OFF), and use SIAH as a new prognostic biomarker to risk stratify patients, detect cancer racial disparities, forecast tumor relapse, and predict patient survival at 1st-line neoadjuvant settings. By targeting SIAH, individualized treatments can be created to allow for increased survival rates in at risk individuals with more aggressive TNBCs. Citation Format: Claire B. Piatak, Taylor N. Drake, Ashleigh Hannah, Jonathan Baker, Caroline L. Dasom, Emily L. Breeding, Janet S. Winston, Billur Samli, Rick Jansen, Michael Danso, Richard A. Hoefer, Amy H. Tang. Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2137.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Survivin expression in ovarian carcinoma and its role as apoptotic inhibitor and prognostic predictor

Background: Most ovarian cancers are diagnosed at advanced stages due to the lack of specific symptoms and lack of efficient screening methods. It is very important to examine prognostic predictor factors to increase survival rates. Survivin is a protein that plays a key role in inhibiting the process of programmed cell death or apoptosis, which will cause increased mitosis and cell proliferation as well as a worse prognosis. This study aims to prove the role of survivin as an inhibitor of apoptosis and predict prognosis by proving the existence of an association between survivin expression and mitotic index and proving the difference in survivin expression in type I and type II ovarian carcinoma. Methods: A cross-sectional analytical observational study, a total sample of 40, taken from surgical specimens from ovarian carcinoma patients whose tissues were examined at the Anatomical Pathology Laboratory Faculty of Medicine Universitas Udayana/ Prof. dr. I G.N.G. Ngoerah Hospital Denpasar. Histopathological diagnosis and mitotic index were performed using H &amp; E staining. Survivin expression was evaluated by immunohistochemical staining. Data analysis using chi-square test, significance value of p &lt; 0.05. Results: The mean age for type I ovarian carcinoma was 47.75 ± 11.50, and type II was 55.30 ± 6.11. The chi-square test shows a significant difference in survivin expression (p = 0.009) and in mitotic index (p = 0.001) of type I and type II ovarian carcinoma. A significant association was also found between survivin expression and mitotic index in type I (p = 0.046) and in type II ovarian carcinoma (p = 0.018). Conclusion: There was a significant association between survivin expression and mitotic index and differences in survivin expression in type I and type II ovarian carcinoma.

Factors associated with recurrence in patients with oral cancer in Mongolia

IntroductionIn Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy.MethodA retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia’s Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences’ Research Ethics Committee approved the project.ResultsThe findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24–11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence.ConclusionThis study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.

The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.

Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique

To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. Step-by-step description of the surgical technique with narrated video footage. Academic tertiary hospital. Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. Step by step educational video. The post-operative course was uneventful and the patient was discharge 24 hours after surgery. Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

Evaluation of treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy accompanied by the G-8 geriatric score: TROD13–003 multicenter study

IntroductionThe choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. Materials and MethodsPatients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan–Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. ResultsA total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65–96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DiscussionRadiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.

N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

High-Risk Congenital Heart Disease in Pregnancy.

High-risk congenital heart disease (CHD) in pregnancy presents a complex clinical challenge. With improved medical care and increased survival rates, a growing population of adults with complex CHD are surviving to adulthood, including women of reproductive age. This chapter focuses on risk stratification and management of pregnant women with high-risk CHD, emphasizing the importance of considering both anatomical and physiological complexity. Maternal physiological changes, such as blood volume increase, cardiac output changes, and alterations in vascular resistance, can significantly impact high-risk CHD patients. Management of high-risk CHD in pregnancy necessitates a multidisciplinary approach and individualized care.