Cancer diagnosis & prognosis最新文献

{"title":"Cachexia Index Is a Prognostic Indicator in Patients With Metastatic Urothelial Carcinoma Treated With Systemic Chemotherapy.","authors":"Yoshihisa Mimura, Taku Naiki, Yosuke Sugiyama, Yoshihiko Tasaki, Kunihiro Odagiri, Toshiki Etani, Takashi Nagai, Moeko Iida, Yuka Kimura, Nanami Ito, Yuji Hotta, Takahiro Yasui, Yoko Furukawa-Hibi","doi":"10.21873/cdp.10351","DOIUrl":"10.21873/cdp.10351","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy.</p><p><strong>Patients and methods: </strong>The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan-Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS).</p><p><strong>Results: </strong>At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05].</p><p><strong>Conclusion: </strong>CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499777","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":"Comparing the Effectiveness of Afatinib and Osimertinib for Patients With PD-L1-positive <i>EGFR</i>-mutant Non-small Cell Carcinoma.","authors":"Minehiko Inomata, Yosuke Kawashima, Ryota Saito, Daisuke Morinaga, Hitomi Nogawa, Masamichi Sato, Yohei Suzuki, Satoru Yanagisawa, Takashi Kikuchi, Daisuke Jingu, Naruo Yoshimura, Toshiyuki Harada, Eisaku Miyauchi","doi":"10.21873/cdp.10357","DOIUrl":"10.21873/cdp.10357","url":null,"abstract":"<p><strong>Background/aim: </strong>Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective for treating non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, higher tumor programmed death ligand-1 (PD-L1) expression is associated with a poor response to EGFR-TKIs, and information on the comparison between afatinib and osimertinib in PD-L1-positive EGFR-mutant NSCLC is scarce.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed data of patients with PD-L1-positive EGFR-mutant NSCLC to compare the effectiveness of afatinib and osimertinib.</p><p><strong>Results: </strong>A total of 177 patients were included in the study. The Cox proportion hazard model was adjusted for age, sex, performance status, EGFR mutation status, PD-L1 expression level, and brain metastasis, revealing that there was no significant difference in risk for progression [hazard ratio (HR)=0.99, 95% confidence interval (CI)=0.64-1.53] or death (HR=0.96, 95% CI=0.54-1.73) between afatinib and osimertinib.</p><p><strong>Conclusion: </strong>In conclusion, the EGFR-TKI treatment duration and overall survival after the treatment with afatinib or osimertinib were similar in patients with PD-L1-positive EGFR-mutant NSCLC in the present study.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499802","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":"Therapeutic Resistance in G-CSF Producing Lung Cancer With <i>EGFR</i> Mutation.","authors":"Koki Ito, Kyoichi Kaira, Hisao Imai, Ayako Shiono, Kosuke Hashimoto, O U Yamaguchi, Hiroshi Kagamu","doi":"10.21873/cdp.10359","DOIUrl":"10.21873/cdp.10359","url":null,"abstract":"<p><strong>Background/aim: </strong>Granulocyte colony-stimulating factor (G-CSF)-producing neoplasms are relatively rare; however, little is known on the clinical features of G-CSF-producing lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations.</p><p><strong>Case report: </strong>A 66-year-old female was definitively diagnosed with G-CSF-producing lung cancer that was positive for EGFR mutations. She repeatedly received epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib and afatinib. However, she developed resistance to these molecular-targeting drugs within 2 to 3 months after immediate shrinkage. Thus, the patient was treated with chemoimmunotherapy including bevacizumab, and demonstrated a slight survival benefit.</p><p><strong>Conclusion: </strong>Overall, G-CSF-producing lung cancers positive for EGFR mutations were resistant to different treatment modalities. Clinicians should be attentive to the potential resistance of G-CSF-producing EGFR mutant lung cancer to EGFR-TKI therapy.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499748","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":"Age Is a Risk Factor for Olaparib Dose Modification and Discontinuation in Patients With Ovarian Cancer.","authors":"Hiroaki Inui, Masayasu Sato, Hiroyuki Yoshida","doi":"10.21873/cdp.10346","DOIUrl":"10.21873/cdp.10346","url":null,"abstract":"<p><strong>Background/aim: </strong>Olaparib, a poly (ADP-ribose) polymerase inhibitor, is widely used as maintenance therapy for ovarian cancer. Dose modification, such as dose reduction and treatment interruption, are frequently performed to manage adverse events (AEs) of olaparib. By identifying patients at high risk for dose modification before administration, interventions related to appropriate control of AEs can be implemented. This study aimed to evaluate risk factors of olaparib dose modification and its clinical usefulness.</p><p><strong>Patients and methods: </strong>Sixty patients with ovarian cancer who received olaparib were included in this retrospective cohort study. Associations between patients' characteristics and dose modification were evaluated by multivariate logistic regression analysis. We also examined whether risk factors of dose modification were associated with treatment discontinuation due to AEs.</p><p><strong>Results: </strong>Twenty-five (41.7%) patients required dose modification. Patients who required dose modification were significantly older (p=0.018) and tended to be more underweight (p=0.078) than those who did not require dose modification. In multivariate analysis, increasing age was significantly associated with dose modification (odds ratio=1.056; 95% confidence interval=1.002-1.112; p=0.034). The optimal cutoff of age as a risk factor for dose modification, calculated from receiver operating characteristic curves, was 65.0 years. Patients aged 65.0 years and older were significantly more likely to discontinue olaparib owing to AEs (p=0.0437).</p><p><strong>Conclusion: </strong>Age is a risk factor of olaparib dose modification due to AEs. Older patients, who frequently require dose modification, are more likely to discontinue olaparib, suggesting that strict management of AEs is particularly necessary in this patient group.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499774","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":"BMP Signaling Is a Prognostic Marker in Patients With Colorectal Cancer and Associates With Frailty.","authors":"Shohei Sawata, Shota Shimizu, Yoshiaki Matsumi, Yusuke Kono, Kyoichi Kihara, Manabu Yamamoto, Teruhisa Sakamoto, Yoshihisa Umekita, Yoshiyuki Fujiwara","doi":"10.21873/cdp.10341","DOIUrl":"10.21873/cdp.10341","url":null,"abstract":"<p><strong>Background/aim: </strong>Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily of ligands and have been shown to promote or suppress colorectal cancer (CRC) growth. Developing treatments that target BMPs is challenging due to their multiple roles, including involvement in the inflammatory response and nutritional status. The present study evaluated the prognostic value of BMP-4, which is believed to be highly expressed in CRC, and its correlation with inflammatory and nutrition statuses in patients with CRC.</p><p><strong>Materials and methods: </strong>We analyzed BMP-4 expression in tumor tissues from 144 patients who underwent CRC surgery using immunohistochemistry and evaluated the relationship between BMP-4 levels and clinical outcomes.</p><p><strong>Results: </strong>Kaplan-Meier analysis revealed that patients with high expression levels of BMP-4 exhibited a shorter overall survival rate than those with low levels of expression. Multivariate analysis revealed that BMP-4 expression was an independent prognostic factor for overall survival and death from other diseases in CRC patients. Furthermore, high BMP-4 expression was significantly correlated with high C-reactive protein/Albumin ratio, sarcopenia, and osteopenia.</p><p><strong>Conclusion: </strong>BMP-4 is a significant prognostic factor in CRC, particularly in predicting death from other diseases, while also showing associations with inflammatory and nutritional statuses.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499776","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":"Tubular Carcinoma of the Breast: The Possibility to Omit Sentinel Lymph Node Biopsy.","authors":"Sae Yamane, Akira Matsui, Ayako Nakashoji, Manami Sasahara, Yuya Murata, Takayuki Kinoshita","doi":"10.21873/cdp.10344","DOIUrl":"10.21873/cdp.10344","url":null,"abstract":"<p><strong>Background/aim: </strong>Tubular breast carcinoma, classified as a special type of invasive cancer, has a good prognosis. This study aimed to retrospectively investigate the clinical and pathological characteristics of 32 tubular carcinoma cases enrolled at our institution, with a focus on exploring the potential for treatment de-escalation.</p><p><strong>Patients and methods: </strong>The study included all patients diagnosed with tubular breast carcinoma at our hospital between January 2005 and December 2021. In addition, 549 patients with ductal carcinoma in situ (DCIS) and 1,524 patients with stage I and II invasive cancers [not otherwise specified (NOS)] were selected for comparison.</p><p><strong>Results: </strong>All participants were female, with an average age of 54.4 years. The median follow-up duration was 64 months. The median tumor diameter was 7 mm, and all cases were Luminal A type. Moreover, no lymph vascular invasion was observed in any case, and no local recurrence, distant metastasis, or death occurred. The sentinel lymph node positive rate was 0% in the tubular carcinoma group, significantly lower than that in the NOS group (25.5%, p=0.0019) and not significantly different from that in the DCIS group (0.2%). The tubular carcinoma group tended to have better overall survival (OS) and disease-free survival (DFS) than the NOS group. Furthermore, the tubular carcinoma group was not inferior in OS and DFS compared to the DCIS group.</p><p><strong>Conclusion: </strong>Lymph node metastasis rate, OS, and DFS of the tubular carcinoma group are comparable to those of the DCIS group. Sentinel lymph node biopsy for tubular carcinoma can be omitted with an accurate preoperative diagnosis.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499821","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":"Laryngeal Preservation Rate and Salvage Therapy Following Initial Recurrence in a Real-world Setting After Definitive Radiation Therapy in Patients With Locally Advanced Laryngeal Squamous Cell Carcinoma.","authors":"Atsuto Katano, Takeshi Maemura, Masanari Minamitani, Shingo Ohira, Hideomi Yamashita","doi":"10.21873/cdp.10342","DOIUrl":"10.21873/cdp.10342","url":null,"abstract":"<p><strong>Background/aim: </strong>The larynx plays a pivotal role in vocalization and airway protection, and laryngeal cancer manifests through various symptoms. Contemporary strategies focus on laryngeal preservation, particularly through non-surgical modality therapies that utilize radiotherapy. The aim of this study was to assess the laryngeal preservation rate after definitive radiation therapy in patients with locally advanced laryngeal squamous cell carcinoma and investigate salvage therapy subsequent to the initial recurrence in a real-world context.</p><p><strong>Patients and methods: </strong>Analysis included a total of 40 patients with locally advanced laryngeal squamous cell carcinoma who were treated with definitive radiotherapy in the University of Tokyo Hospital. Treatment involved external beam radiotherapy (70 Gy in 35 fractions) with elective nodal irradiation. The main study outcomes were assessment of survival, overall survival, local control, and the factors influencing laryngeal preservation.</p><p><strong>Results: </strong>The patients exhibited a median age of 64.5 years, and 80% of them were men. Chemotherapy was administered to 82.5% of the patients. The 3-year overall survival, progression-free, and laryngeal preservation survival rates were 86.3%, 66.8%, and 78.4%, respectively. Univariate and multivariate analyses identified chemotherapy to be significantly associated with favorable laryngeal preservation survival (p<0.001).</p><p><strong>Conclusion: </strong>Definitive radiotherapy results in favorable outcomes for laryngeal preservation in locally advanced laryngeal squamous cell carcinoma. This study emphasizes the importance of chemotherapy in comprehensive patient management. Nevertheless, larger prospective studies are crucial to validate and optimize therapeutic approaches for this condition.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499740","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":"Comprehensive Analysis of Craniopharyngioma: Epidemiology, Clinical Characteristics, Management Strategies, and Role of Radiotherapy.","authors":"Amir Mushtaq, Mohsin Fayaz, Abdul Rashid Bhat, Abbas F Abdul Hussein, Gianluca Ferini, Giuseppe Emmanuele Umana, Gianluca Scalia, Feroze Ahmad Mir, Aizul Khursheed, Bipin Chaurasia","doi":"10.21873/cdp.10358","DOIUrl":"10.21873/cdp.10358","url":null,"abstract":"<p><strong>Background/aim: </strong>Craniopharyngiomas pose challenges in diagnosis and management due to their rare occurrence and diverse clinical manifestations. This study aimed to provide a comprehensive analysis of cranio-pharyngioma, including its epidemiological trends, clinical presentations, radiological characteristics, surgical interventions, and the role of radiotherapy.</p><p><strong>Patients and methods: </strong>A retrospective observational study was conducted on 23 patients diagnosed with craniopharyngioma at our hospital from August 2017 to July 2019. Data regarding demographics, clinical presentation, radiological findings, surgical interventions, and adjuvant therapies were collected and analyzed.</p><p><strong>Results: </strong>Craniopharyngiomas exhibited a bimodal age distribution, with peaks in childhood and late adulthood. Clinical presentations varied between pediatric and adult patients, with headache and nausea/vomiting predominant in children, and visual disturbances and hypogonadism more common in adults. Radiological imaging revealed predominantly suprasellar localization and varying tumor consistency. Surgical resection was the primary treatment modality, with post-operative complications including diabetes insipidus and cerebrospinal fluid leak. Histological analysis showed distinct subtypes, with the adamantinomatous subtype predominant in children and the papillary subtype in adults. Adjuvant radiotherapy was administered in cases of incomplete resection or tumor recurrence.</p><p><strong>Conclusion: </strong>This study provides comprehensive insights into the epidemiology, clinical characteristics, radiological features, surgical interventions, and role of radiotherapy in craniopharyngioma management. Understanding these aspects is crucial for tailoring optimal treatment strategies and improving patient outcomes in this complex clinical scenario.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499803","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 Impact of the Administration of Antibiotics and Proton Pump Inhibitors in Immune Checkpoint Inhibitor Combination Therapy for Advanced Renal Cell Carcinoma.","authors":"Nanaka Katsurayama, Hiroki Ishihara, Ryo Ishiyama, Yuki Nemoto, Takashi Ikeda, Shinsuke Mizoguchi, Takayuki Nakayama, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Hiroaki Shinmura, Yasunobu Hashimoto, Tsunenori Kondo, Toshio Takagi","doi":"10.21873/cdp.10354","DOIUrl":"10.21873/cdp.10354","url":null,"abstract":"<p><strong>Background/aim: </strong>The prognostic impact of the administration of antibiotics and proton pump inhibitors (PPIs) in immune checkpoint inhibitor (ICI) therapy for advanced cancer has recently been documented. However, how these drugs affect the outcomes of first-line ICI combination therapy for advanced renal cell carcinoma (RCC) remains unclear.</p><p><strong>Patients and methods: </strong>We retrospectively evaluated the data of 128 patients with RCC who received first-line ICI combination therapy. The patients were grouped according to their history of antibiotics and PPIs use one month before the initiation of ICI combination therapy. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after ICI combination therapy were compared between patients treated with and without antibiotics or PPIs.</p><p><strong>Results: </strong>Of the 128 patients, 30 (23%) and 44 (34%) received antibiotics and PPIs, respectively. Patients treated with antibiotics exhibited shorter PFS and OS compared to those who did not receive antibiotics (median PFS: 4.9 vs. 16.1 months, p<0.0001; OS: 20.8 vs. 49.0 months, p=0.0034). Multivariate analyses showed that antibiotic administration was an independent predictor of shorter PFS (hazard ratio: 2.54: p=0.0002) and OS (hazard ratio: 2.56: p=0.0067) after adjusting for other covariates. In contrast, there were no significant differences in either PFS or OS between patients who received PPIs and those who did not. (PFS: p=0.828; OS: p=0.105).</p><p><strong>Conclusion: </strong>Antibiotics administration before ICI combination therapy was negatively associated with outcomes of first-line ICI combination therapy for advanced RCC. Therefore, careful monitoring is required for potentially high-risk patients undergoing ICI combination therapy.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499743","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":"Synergy of Rapamycin and Methioninase on Colorectal Cancer Cells Requires Simultaneous and Not Sequential Administration: Implications for mTOR Inhibition.","authors":"Daniel Ardjmand, Motokazu Sato, Qinghong Han, Yutaro Kubota, Kohei Mizuta, Sei Morinaga, Robert M Hoffman","doi":"10.21873/cdp.10338","DOIUrl":"10.21873/cdp.10338","url":null,"abstract":"<p><strong>Background/aim: </strong>Rapamycin inhibits the mTOR protein kinase. Methioninase (rMETase), by degrading methionine, targets the methionine addiction of cancer cells and has been shown to improve the efficacy of chemotherapy drugs, reducing their effective doses. Our previous study demonstrated that rapamycin and rMETase work synergistically against colorectal-cancer cells, but not on normal cells, when administered simultaneously in vitro. In the present study, we aimed to further our previous findings by exploring whether  synergy exists between rapamycin and rMETase when used sequentially against HCT-116 colorectal-carcinoma cells, compared to simultaneous administration, in vitro.</p><p><strong>Materials and methods: </strong>The half-maximal inhibitory concentrations (IC₅₀) of rapamycin alone and rMETase alone against the HCT-116 human colorectal-cancer cell line were previously determined using the CCK-8 cell viability assay (11). We then examined the efficacy of rapamycin and rMETase, both at their IC₅₀, administered simultaneously or sequentially on the HCT-116 cell line, with rapamycin administered before rMETase and vice versa.</p><p><strong>Results: </strong>The IC₅₀ for rapamycin and rMETase, determined from previous experiments (11), was 1.38 nM and 0.39 U/ml, respectively, of HCT-116 cells. When rMETase was administered four days before rapamycin, both at the IC₅₀, there was a 30.46% inhibition of HCT-116 cells. When rapamycin was administered four days before rMETase, both at the IC₅₀, there was an inhibition of 41.13%. When both rapamycin and rMETase were simultaneously administered, both at the IC₅₀, there was a 71.03% inhibition.</p><p><strong>Conclusion: </strong>Rapamycin and rMETase have synergistic efficacy against colorectal-cancer cells in vitro when administered simultaneously, but not sequentially.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499746","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}