Cancer treatment and research communications最新文献

{"title":"Prostate cancer knowledge and barriers to screening among men at risk in northern Tanzania: A community-based study","authors":"Bartholomeo Nicholaus Ngowi ,&nbsp;Alex Mremi ,&nbsp;Orgeness Jasper Mbwambo ,&nbsp;Modesta Paschal Mitao ,&nbsp;Mramba Nyindo ,&nbsp;Kien Alfred Mteta ,&nbsp;Blandina Theophil Mmbaga","doi":"10.1016/j.ctarc.2024.100811","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100811","url":null,"abstract":"<div><h3>Background</h3><p>Although prostate cancer (Pca) screening plays important role in early diagnosis and reduction of mortality, Tanzanian men are relatively unscreened. We aimed to investigate Pca knowledge level and barriers to screening among at-risk men in northern Tanzania.</p></div><div><h3>Methods</h3><p>This community-based survey was conducted in northern Tanzania from May to September 2022, involving men age ≥40 years. Participants were invited by announcing in local churches, mosques, brochures, and social media groups. Participants attended a nearby health facility where survey questionnaires were administered. Knowledge level was measured on the Likert scale and scored as poor (&lt;50 %) or good (≥50 %).</p></div><div><h3>Results</h3><p>A total of 6205 men with a mean age of 60.23 ± 10.98 years were enrolled in the study. Of these, 586 (9.5 %) had ever been screened for Pca. Overall, 1263 men (20.4 %) had good knowledge of Pca. Having health insurance, knowing at least 1 risk factor or symptoms of Pca, and hospital as the source of Pca information were significantly associated with ever being screened. The most common reasons for not being screened were a belief that they are healthy (<em>n</em> = 2983; 53.1 %), that Pca is not a serious disease (<em>n</em> = 3908; 69.6 %), and that digital rectal examination (DRE) as an embarrassing (<em>n</em> = 3634; 64.7 %) or harmful (<em>n</em> = 3047; 54.3 %) procedure.</p></div><div><h3>Conclusion</h3><p>Having Pca knowledge, health insurance and hospital source of information were correlated with increased screening. False beliefs about DRE and the seriousness of Pca had negative effects on screening. Increasing community knowledge and universal health coverage would improve uptake of Pca screening.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"39 ","pages":"Article 100811"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000236/pdfft?md5=278085955eb28f5b88051eb990ce9c00&pid=1-s2.0-S2468294224000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140341213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of safety and tolerability of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: Results of an open-label, randomized, multicenter, phase IIIB ESCAPE trial","authors":"Dilyara Kaidarova ,&nbsp;Edvard Zhavrid ,&nbsp;Oxana Shatkovskaya ,&nbsp;Aliaksandr Prokharau ,&nbsp;Nina Akhmed ,&nbsp;Dauren Sembayev ,&nbsp;Zhanna Rutzhanova ,&nbsp;Alexandr Ivankov","doi":"10.1016/j.ctarc.2024.100817","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100817","url":null,"abstract":"<div><h3>Aim</h3><p>To assess the safety and tolerability of subcutaneous (SC) trastuzumab (Herceptin) administered either with a single-use injection device (SID) or manually from a vial using a hand-held syringe.</p></div><div><h3>Methods</h3><p>The ESCAPE trial (NCT02194166) included 90 women aged 18 years or older with HER2-positive early breast cancer who underwent surgical treatment and completed (neo) adjuvant chemotherapy and radiotherapy (if indicated). Patients enrolled in the study were first subjected to 4 cycles of trastuzumab IV (8 mg/kg loading dose followed by 6 mg/kg maintenance dose, q3w) prior to being randomized into groups: [A] SC trastuzumab (fixed dose 600 mg, q3w) administered through a hand-held syringe followed by 7 cycles of SC trastuzumab administered with an SID or [B] the reverse sequence.</p></div><div><h3>Results</h3><p>Patient-reported outcomes revealed that 78 (94.0 % [95 % CI: 90.4–99.0]) out of 83 patients preferred SC trastuzumab over IV trastuzumab, among whom 28 patients indicated a strong preference. Sixteen out of 17 HCPs (94.1 %) were very satisfied with the use of SC trastuzumab, while 1/17 (5.9 %) remained uncertain. The mean time spent for IV vs. SC trastuzumab administration, including pre- and postinjection procedures, was 93.8 and 22 min, respectively. A total of 49 (54.4 %) patients reported 164 AEs.</p></div><div><h3>Conclusions</h3><p>In this trial, SC trastuzumab was preferred over IV trastuzumab. The duration of SC trastuzumab administration was significantly shorter than that of IV trastuzumab, saving patients and HCPs time. Safety and efficacy results were consistent with other published trials and were not associated with any new safety signal.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"40 ","pages":"Article 100817"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000297/pdfft?md5=082e01b0512576154bebb1218d234e96&pid=1-s2.0-S2468294224000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ctDNA-based minimal residual disease detection in lung cancer patients treated with curative intended chemoradiotherapy using a clinically transferable approach","authors":"Lærke Rosenlund Nielsen ,&nbsp;Simone Stensgaard ,&nbsp;Peter Meldgaard ,&nbsp;Boe Sandahl Sorensen","doi":"10.1016/j.ctarc.2024.100802","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100802","url":null,"abstract":"<div><h3>Background</h3><p>Reliable biomarkers are needed to identify tumor recurrence of non-small cell lung cancer (NSCLC) patients after chemoradiotherapy (CRT) with curative intent. This could improve consolidation therapy of progressing patients. However, the approach of existing studies has limited transferability to the clinic.</p></div><div><h3>Materials and methods</h3><p>A retrospective analysis of 135 plasma samples from 56 inoperable NSCLC patients who received CRT with curative intent was performed. Plasma samples collected at baseline, at the first check-up (average 1.6 months post-RT), and at the second check-up (average 4.5 months post-RT) were analyzed by deep sequencing with a commercially available cancer personalized profiling strategy (CAPP-Seq) using a tumor-agnostic approach.</p></div><div><h3>Results</h3><p>Detection of circulating tumor DNA (ctDNA) at 4.5 months after therapy was significantly associated with higher odds of tumor recurrence (OR: 5.4 (CI: 1.1–31), Fisher's exact test: <em>p</em>-value = 0.022), and shorter recurrence-free survival (RFS) (HR: 4.1 (CI: 1.7–10); log-rank test: <em>p</em>-value = 9e-04). In contrast, detection of ctDNA at 1.6 months after therapy was not associated with higher odds of tumor recurrence (OR: 2.7 (CI: 0.67–12), Fisher's exact test: <em>p</em>-value = 0.13) or shorter RFS (HR: 1.5 (CI: 0.67–3.3); log-rank test: <em>p</em>-value = 0.32).</p></div><div><h3>Conclusion</h3><p>This study demonstrates that the detection of ctDNA can be used to identify minimal residual disease 4.5 months after CRT in NSCLC patients using a commercially available kit and a tumor-agnostic approach. Furthermore, the time point of collecting the plasma sample after CRT has decisive importance for the prognostic value of ctDNA.</p></div><div><h3>Micro abstract</h3><p>This study analysed 135 plasma samples from 56 NSCLC patients treated with curative intent chemoradiotherapy using a tumor-agnostic approach. Detecting ctDNA at 4.5 months post-treatment was linked to higher recurrence odds, indicating ctDNA's potential as a biomarker for identifying residual disease after treatment with curative intent. Importantly, the study emphasizes the importance of timing for accurate ctDNA analysis results.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"39 ","pages":"Article 100802"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000145/pdfft?md5=47b4ed51e233a53acd993e7bdb48e2c2&pid=1-s2.0-S2468294224000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of dietary sugars in cancer risk: A comprehensive review of current evidence","authors":"Nazmul Hasan ,&nbsp;Omid Yazdanpanah ,&nbsp;Barbod Khaleghi ,&nbsp;David J. Benjamin ,&nbsp;Arash Rezazadeh Kalebasty","doi":"10.1016/j.ctarc.2025.100876","DOIUrl":"10.1016/j.ctarc.2025.100876","url":null,"abstract":"<div><h3>Goal of the review</h3><div>The objective of this review is to conduct a thorough examination of the current evidence regarding the correlation between dietary sugar intake and cancer risk. This will encompass the biological mechanisms, the diverse effects of various sugar types, and the potential implications for cancer treatment and dietary recommendations.</div></div><div><h3>Introduction</h3><div>Nutritional and epidemiological studies now focus much on the relationship between sugar intake and cancer. The data is still conflicting even if some studies imply that excessive sugar intake can help cancer develop by means of insulin resistance and chronic inflammation.</div></div><div><h3>Discussion</h3><div>Through processes such as insulin resistance, inflammation, and angiogenesis, dietary sugars can impact carcinogenesis. Fructose increases angiogenesis by VEGF overexpression while glucose stimulates cancer cell growth by the Warburg effect. Contradicting data on the contribution of sugar to cancer emphasizes the need of consistent research techniques to simplify these dynamics. Reducing added sugar consumption in cancer prevention and management is especially crucial given that sugar affects immune function and treatment resistance, which could lead to new therapeutic targets.</div></div><div><h3>Conclusion</h3><div>High sugar intake is linked to mechanisms such as the Warburg effect, insulin resistance, and chronic inflammation, which may contribute to cancer risk under specific conditions. However, the evidence is not universally conclusive, and additional large-scale, long-term research are required to better understand these processes. To help in cancer prevention and management, public health guidelines should emphasize reducing added sugar consumption and promoting a balanced diet rich in natural foods.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100876"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143223196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial oncolytic therapy as a novel approach for cancer treatment in humans","authors":"Sikander Ali ,&nbsp;Asma Mehboob ,&nbsp;Muhammad Arshad ,&nbsp;Khayala Mammadova ,&nbsp;Muhammad Usman Ahmad","doi":"10.1016/j.ctarc.2025.100892","DOIUrl":"10.1016/j.ctarc.2025.100892","url":null,"abstract":"<div><div>Cancer is the leading cause of death worldwide. Conventional cancer therapies, such as chemotherapy, radiation therapy, and immunotherapy often face certain limitations in treating cancer, such as toxicity, resistance, and ineffectiveness against different cancer types. Therefore, there is an urgent need for alternative treatment strategies. One emerging area of interest is the use of bacterial oncolytic therapy. It employs the natural properties of bacteria to target and destroy cancer cells. Both natural and genetically modified bacterial strains have shown potential to target the hypoxic regions of tumors, which are often resistant to conventional treatments. These bacteria also produce therapeutic molecules that induce cancer cell death. Furthermore, they can stimulate immune responses against tumors, making them helpful in developing cancer vaccines and exploiting antitumor bacterial metabolites. The versatility of bacterial oncolytic therapy extends beyond direct tumor targeting. It can be combined with conventional methods to enhance overall treatment efficacy. Moreover, bacteria can also serve as delivery vehicles for anticancer drugs, ensuring more precise targeting and reduced side effects. Different bacterial genera, such as <em>Salmonella, Clostridium, Bifidobacterium,</em> and <em>Listeria</em>, have demonstrated significant anticancer potential. This review aims to provide a comprehensive overview of bacterial oncolytic therapy, exploring its various applications and potential in conjunction with traditional cancer treatments.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100892"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the association between the CASP8rs1045485 and SOD2 rs4880 single nucleotide polymorphisms (SNPs) with breast cancer","authors":"Seyedeh Rojin Shikholeslami,&nbsp;Fatemeh Keshavarzi","doi":"10.1016/j.ctarc.2024.100835","DOIUrl":"10.1016/j.ctarc.2024.100835","url":null,"abstract":"<div><h3>Introduction</h3><p>Single nucleotide polymorphisms (SNPs) have been identified as prognostic markers that can influence the response to chemotherapy and, ultimately, the outcome of the disease. The objective of this study is to investigate the association between the rs1045485 and rs4880 variants and breast cancer.</p></div><div><h3>Methods</h3><p>Ninety-nine cases and 81 healthy individuals (over 60 years old) were recruited from Iranian population. Genotyping of the rs1045485 and rs4880 polymorphisms was determined using the PCR-RFLP molecular method. The obtained results were then evaluated using the SPSS 23.0, odds ratios (ORs) with 95 % confidence intervals (95 %CIs).</p></div><div><h3>Results</h3><p>The average age of the subjects was 50.17± 1.8 years, with age ranging from 40 to 76 years. Additionally, more patients were in stage and grade 2 of the disease. Furthermore, 51.73 %, 53.24 % and 41.48 % of patients tested positive for ER, PR and HER2 status, respectively. The odds ratios of the genotypes studied for each of the two variants were not statistically significant. Additionally, all models (dominant, codominant, recessive and over dominant) also indicated that this difference was not significant (<em>p</em> &gt; 0.05). Investigation of the association between the <em>CASP8</em>rs1045485 and <em>SOD2</em> rs4880 variants with clinicopathological status were not revealed a significant relationship. The Hardy-Weinberg test showed that the evaluated population was balanced (<em>p</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>In the studied models of both polymorphisms, no significant correlation was found between the genotypes and the conditions of estrogen, progesterone and Her2 receptors, as well as the stage and grade of the disease.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"40 ","pages":"Article 100835"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000479/pdfft?md5=28204bba0ca17932a994555216733672&pid=1-s2.0-S2468294224000479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of large amino acid transporter type 1 (LAT1) expression in pulmonary adenocarcinoma: A tissue microarray study","authors":"Azusa Terao ,&nbsp;Hironori Ninomiya ,&nbsp;Kengo Takeuchi","doi":"10.1016/j.ctarc.2024.100814","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100814","url":null,"abstract":"<div><h3>Background</h3><p>Large amino acid transporter type 1 (LAT1) provides cancer cells with essential amino acids for both protein synthesis and cell growth and may predict patient prognosis. Additionally, LAT1 inhibition can be a therapeutic target. This study aimed to examine the prognostic significance of LAT1 expression in lung cancer, paying special attention to adenocarcinoma subtypes.</p></div><div><h3>Methods</h3><p>Tissue microarrays (TMA) of 1,560 total cores obtained from surgically resected lung cancer specimens between 1995 and 2008 at our hospital were used. Overall, 795 cases of adenocarcinoma were identified, and 717 underwent further evaluation. Immunohistochemical staining of whole slides and TMA cores were assessed to set H-score cutoff value.. Immunohistochemical expression of LAT1 was examined based on the subtypes of adenocarcinoma. Statistical analyses explored the prognostic significance of LAT1.</p></div><div><h3>Results</h3><p>Adenocarcinoma accounted for 71.8% of all cases (<em>n</em> = 795), and 216 cases (27.1%) expressed LAT1. The 795 cases were categorized into five subtypes: lepidic (<em>n</em> = 29, 3.6%), papillary (<em>n</em> = 601, 75.6%), acinar (<em>n</em> = 58, 7.3%), and solid (<em>n</em> = 9, 1.1%); 717 of the 795 cases were further assessed according to the exclusion criteria. The LAT1-positive ratio increased as the architectural grade increased. Notably, in papillary adenocarcinoma, the LAT1-positive group had significantly lower overall survival compared to the negative group (10-year survival: 45.6% vs. 60.8%, <em>p</em> &lt; 0.001).</p></div><div><h3>Conclusion</h3><p>LAT1 expression was higher in high-grade subtypes of pulmonary adenocarcinoma. Moreover, LAT1 expression is useful for predicting prognosis, particularly in papillary adenocarcinoma, facilitating prognostic stratification of papillary adenocarcinoma.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"39 ","pages":"Article 100814"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000261/pdfft?md5=35ae997d2b2534a82c44ea8bb7694380&pid=1-s2.0-S2468294224000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of sentinel lymph node biopsy and bilateral pelvic nodal dissection using methylene blue dye in early-stage operable cervical cancer—A prospective study","authors":"Vijaya Lakshmi Vemula Venkata ,&nbsp;Narendra Hulikal ,&nbsp;Amit Kumar Chowhan","doi":"10.1016/j.ctarc.2024.100816","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100816","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate the effectiveness of methylene blue dye in detecting sentinel lymph nodes (SLNs) in women with early-stage operable (defined as FIGO I-IIA) cervical cancer. It also aims to evaluate procedural challenges and accuracy.</p></div><div><h3>Method</h3><p>This prospective study, which focused on 20 women with early-stage cervical cancer, was carried out between June 2016 and December 2017. These patients had SLN mapping with methylene blue dye injections and thorough examinations, including imaging. All patients underwent radical hysterectomy and complete bilateral pelvic lymphadenectomy. No additional investigation was done on the lymph node in cases where a metastasis was found in the first H&amp;E-stained segment of the sentinel node.</p></div><div><h3>Result</h3><p>20 patients were included in the analysis. The median age of the subjects was 53, and 95 % of them had squamous cell carcinoma. 90 % of the time, the identification of SLNs was effective, and 55 SLNs were found, of which 52.7 % were on the right side of the pelvis and 47.3 % on the left. The obturator group had the most nodes, followed by the external and internal iliac groups in descending order of occurrence. Metastasis was detected in 3 patients, resulting in a sensitivity of 100 % and a specificity of 93.75 % for SLN biopsy. Notably, no false-negative SLNs were found. Complications related to methylene blue usage included urine discoloration in 30 % of patients.</p></div><div><h3>Conclusion</h3><p>This trial highlights the promising efficacy and safety of methylene blue dye alone for SLN identification in early-stage operable cervical cancer, with a notably higher success rate. Despite limitations like a small sample size, healthcare professionals and researchers can build upon the insights from this study to enhance cervical cancer management.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"39 ","pages":"Article 100816"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000285/pdfft?md5=32abd5744810eab1d50c7068a59119c2&pid=1-s2.0-S2468294224000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer – a register-based study","authors":"Anders S. Eriksson ,&nbsp;Henry Eriksson ,&nbsp;Per-Olof Hansson ,&nbsp;Kurt Svärdsudd","doi":"10.1016/j.ctarc.2024.100820","DOIUrl":"10.1016/j.ctarc.2024.100820","url":null,"abstract":"<div><h3>Background</h3><p>Several studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation.</p></div><div><h3>Methods</h3><p>Data on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (<em>n</em>= 1,216) during the study period were labeled cases and those who did not (<em>n</em>= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register.</p></div><div><h3>Results</h3><p>Hazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59–0.85; <em>p</em>= 0.0002) and men (HR 0.61; 95 % CI 0.52–0.72; <em>p</em> &lt; 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four.</p></div><div><h3>Conclusion</h3><p>Use of warfarin early after diagnosis in patients with CRC was associated with improved survival.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"40 ","pages":"Article 100820"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000327/pdfft?md5=dcb36b9fef1eb26c354c6a7eed173534&pid=1-s2.0-S2468294224000327-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a c-MET x CD137 bispecific antibody for targeted immune agonism in cancer immunotherapy","authors":"Hong Zhang ,&nbsp;Qun Wang ,&nbsp;Sireesha Yalavarthi ,&nbsp;Lukas Pekar ,&nbsp;Steven Shamnoski ,&nbsp;Liufang Hu ,&nbsp;Laura Helming ,&nbsp;Stefan Zielonka ,&nbsp;Chunxiao Xu","doi":"10.1016/j.ctarc.2024.100805","DOIUrl":"https://doi.org/10.1016/j.ctarc.2024.100805","url":null,"abstract":"<div><h3>Background</h3><p>Targeting the costimulatory receptor CD137 has shown promise as a therapeutic approach for cancer immunotherapy, resulting in anti-tumor efficacy demonstrated in clinical trials. However, the initial CD137 agonistic antibodies, urelumab and utomilumab, faced challenges in clinical trials due to the liver toxicity or lack of efficacy, respectively. Concurrently, c-MET has been identified as a highly expressed tumor-associated antigen (TAA) in various solid and soft tumors.</p></div><div><h3>Methods</h3><p>In this study, we aimed to develop a bispecific antibody (BsAb) that targets both c-MET and CD137, optimizing the BsAb format and CD137 binder for efficient delivery of the CD137 agonist to the tumor microenvironment (TME). We employed a monovalent c-MET motif and a trimeric CD137 Variable Heavy domain of Heavy chain (VHH) for the BsAb design.</p></div><div><h3>Results</h3><p>Our results demonstrate that the c-MET x CD137 BsAb provides co-stimulation to T cells through cross-linking by c-MET-expressing tumor cells. Functional immune assays confirmed the enhanced efficacy and potency of the c-MET x CD137 BsAb, as indicated by activation of CD137 signaling, target cell killing, and cytokine release in various tumor cell lines. Furthermore, the combination of c-MET x CD137 BsAb with Pembrolizumab showed a dose-dependent enhancement of target-induced T cell cytokine release.</p></div><div><h3>Conclusion</h3><p>Overall, the c-MET x CD137 BsAb exhibits a promising developability profile as a tumor-targeted immune agonist by minimizing off-target effects while effectively delivering immune agonism. It has the potential to overcome resistance to anti-PD-(L)1 therapies.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"39 ","pages":"Article 100805"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468294224000170/pdfft?md5=596c44fe3b0550f1678bc63b21ca8a9e&pid=1-s2.0-S2468294224000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}