Esin Bayrali Ülker, Esin Çetin Aktaş, Mehmet Fatih Seyhan, Turgay Isbir, Deryanaz Billur, Özlem Timirci-Kahraman
{"title":"Effects of Curcumin and Its Analogue Desmethoxycurcumin on miR-133b and Its Target Gene GSTP-1 in Cisplatin-resistant Ovarian Cancer Cells.","authors":"Esin Bayrali Ülker, Esin Çetin Aktaş, Mehmet Fatih Seyhan, Turgay Isbir, Deryanaz Billur, Özlem Timirci-Kahraman","doi":"10.21873/anticanres.17362","DOIUrl":"https://doi.org/10.21873/anticanres.17362","url":null,"abstract":"<p><strong>Background/aim: </strong>Ovarian cancer, despite being the fifth most common gynecological malignancy, has the highest mortality rate. Recent clinical studies have explored the potential of natural products, like curcumin (CUR), to enhance conventional chemotherapy by targeting multiple cellular pathways. This study aimed to evaluate the effects of CUR and its analog, demethoxycurcumin (DMC), on human ovarian cancer and cisplatin-resistant ovarian cancer cell proliferation and apoptosis. Additionally, we investigated the expression of a candidate gene (GSTP-1), and microRNA (miR-133b) involvement in glutathione metabolism, a potential resistance mechanism in cisplatin-resistant ovarian cancer cells.</p><p><strong>Materials and methods: </strong>Cell proliferation was measured using the WST-1 assay after exposing cisplatin-resistant (A2780cp) and sensitive (A2780) ovarian cancer cell lines to various concentrations of CUR and DMC for different time periods. Apoptosis was quantified using the Annexin V-FITC/PI assay. To understand the underlying mechanisms, we examined the expression levels of GSTP-1 and miR-133b using quantitative RT-PCR.</p><p><strong>Results: </strong>The WST-1 assay revealed that CUR and DMC inhibited cell proliferation in both cell lines, with cisplatin causing a sharper viability decline in A2780cp cells. Annexin V-PI staining detected early apoptosis induced by CUR, DMC, and their combinations in both cell lines at 12 hours, with no necrosis observed. Gene expression analysis showed a significant decrease in GSTP-1 and miR-133b levels in A2780cp cells compared to A2780 cells. The combination treatments, particularly Cur+DMC+Cisplatin, synergistically reduced GSTP-1 and miR-133b expression.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of CUR and DMC to enhance the efficacy of cisplatin in ovarian cancer treatment. The observed decrease in GSTP-1 and miR-133b expression in cisplatin-resistant cells suggests their involvement in drug resistance and highlights their potential as therapeutic targets.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5351-5359"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic Impact of Squamous Cell Carcinoma Antigen During Neoadjuvant Chemotherapy for Patients With Esophageal Squamous Cell Carcinoma Treated With Minimally Invasive Esophagectomy.","authors":"Rikuya Torigoe, Taro Oshikiri, Hironobu Goto, Yasuhumi Koterazawa, Ryuichiro Sawada, Taro Ikeda, Hitoshi Harada, Naoki Urakawa, Hiroshi Hasegawa, Shingo Kanaji, Kimihiro Yamashita, Takeru Matsuda, Yoshihiro Kakeji","doi":"10.21873/anticanres.17374","DOIUrl":"https://doi.org/10.21873/anticanres.17374","url":null,"abstract":"<p><strong>Background/aim: </strong>Squamous cell carcinoma antigen (SCC) is widely used as a tumor marker for esophageal cancer. In this study, we investigated the relationship between SCC and long-term outcomes in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE).</p><p><strong>Patients and methods: </strong>Between 2010 and 2018, 124 patients with ESCC who underwent MIE after NAC (cisplatin plus 5-fluorouracil) were included. Patients were divided into low and high groups based on their pre-NAC SCC level, according to the cut-off value determined using a receiver operating characteristic curve. These two patient groups were further divided into subgroups by receiver operating characteristics according to whether SCC was low or high after NAC.</p><p><strong>Results: </strong>For overall survival (OS), the cut-off value for SCC pre-NAC was 0.9 ng/ml. Ninety-six patients were in the high SCC group (≥0.9 ng/ml) and 28 patients were in the low SCC group (<0.9 ng/ml) prior to NAC. The patients were then divided into pre-NAC/post-NAC SCC subgroups accordingly: low/low SCC (n=7), low/high SCC (n=21), high/low SCC (n=53), and high/high SCC (n=43). The 5-year OS rates were 100%, 66.7%, 50.9%, and 32.6%, respectively. In the multivariate analysis for OS, a high/high pre-NAC/post-NAC SCC status was an independent prognostic factor for poorer OS, along with pathological N stage.</p><p><strong>Conclusion: </strong>For patients with esophageal squamous cell carcinoma treated with NAC followed by MIE, a high SCC level prior to NAC which was also high after NAC was an independent prognostic factor and might contribute to deciding the need for adjuvant therapy.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5485-5493"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung Mo Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman
{"title":"Selective Synergy of Recombinant Methioninase Plus Docetaxel Against Docetaxel-resistant and -sensitive Fibrosarcoma Cells Compared to Normal Fibroblasts.","authors":"Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung Mo Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman","doi":"10.21873/anticanres.17347","DOIUrl":"https://doi.org/10.21873/anticanres.17347","url":null,"abstract":"<p><strong>Background/aim: </strong>Docetaxel combined with gemcitabine is a second-line treatment for soft-tissue sarcoma; however, its effectiveness is limited because of docetaxel resistance. The objective of the present study was to determine the potential of recombinant methioninase (rMETase) to enhance the efficacy of docetaxel on high-docetaxel-resistant human fibrosarcoma cells in vitro.</p><p><strong>Materials and methods: </strong>Docetaxel-resistant HT1080 (DTR-HT1080) human fibrosarcoma cells were established by culturing them in by progressively increasing concentrations of docetaxel from 0.02 to 9 nM in vitro. The IC<sub>50</sub> values for docetaxel and rMETase, as well as the efficacy of their combination, in inhibiting HT1080 human fibrosarcoma cells, DTR-HT1080 cells, and Hs27 normal human fibroblasts were determined. Four experimental groups were examined in vitro: control group without treatment; docetaxel alone; rMETase alone; docetaxel combined with rMETase.</p><p><strong>Results: </strong>The IC<sub>50</sub> of docetaxel for DTR-HT1080 cells was 7.57 nM, compared to the parental HT1080 cells with an IC<sub>50</sub> of 1.68 nM, a 4.5-fold increase. The IC<sub>50</sub> of docetaxel on Hs27 fibroblasts was 4.46 nM. The IC<sub>50</sub> of rMETase on HT1080 cells was 0.75 U/ml (data from [6]). The IC<sub>50</sub> of rMETase on DTR-HT1080 cells was 0.55 U/ml. The IC<sub>50</sub> of rMETase on Hs27 fibroblasts was 0.93 U/ml (data from [6]). Docetaxel (1.68 nM [IC<sub>50</sub>]) plus rMETase (0.75 U/ml [IC<sub>50</sub>]) synergistically reduced the viability of HT1080 cells (p<0.05). In contrast, docetaxel (4.46 nM) plus rMETase (0.93 U/ml) did not reduce the viability of Hs27 fibroblasts, compared to either agent alone. The combination of rMETase (0.55 U/ml [IC<sub>50</sub>]) and docetaxel (1.68 nM [IC<sub>50</sub> of the parental cells]) overcame docetaxel resistance of DTR-HT1080 cells, resulting in an inhibition of 48.1% compared to docetaxel alone (6.8%) or rMETase alone (37.5%) (p<0.05). rMETase thus increased the efficacy of docetaxel 7-fold on docetaxel-resistant human fibrosarcoma cells.</p><p><strong>Conclusion: </strong>The combination of docetaxel and rMETase was synergistic on HT1080 fibrosarcoma cells, but not normal fibroblasts. rMETase plus docetaxel synergistically reduced the high docetaxel resistance of DTR-HT1080 cells. The present results indicate the clinical potential of rMETase to reduce docetaxel resistance in soft-tissue sarcoma patients in the future.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5207-5213"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ivermectin Enhances Paclitaxel Efficacy by Overcoming Resistance Through Modulation of <i>ABCB1</i> in Non-small Cell Lung Cancer.","authors":"Anna Hayashi, Koichiro Kamio, Akihiko Miyanaga, Keisuke Yoshida, Rintaro Noro, Kuniko Matsuda, Takehiro Tozuka, Miwako Omori, Mariko Hirao, Aya Fukuizumi, Kakeru Hisakane, Susumu Takeuchi, Masaru Matsumoto, Kazuo Kasahara, Takanori Amano, Kazufumi Honda, Masahiro Seike","doi":"10.21873/anticanres.17355","DOIUrl":"https://doi.org/10.21873/anticanres.17355","url":null,"abstract":"<p><strong>Background/aim: </strong>Chemoresistance to paclitaxel (PTX) significantly ameliorates therapeutic efficacy in patients with non-small cell lung cancer (NSCLC), especially in advanced stages, deteriorating the progression free and overall survival rates. One of the critical mechanisms contributing to drug resistance is the excretion of PTX from target cells via efflux pumps. Ivermectin was developed as a bactericidal agent against parasites; however, it has recently been shown to inhibit the proliferation of human cancer cells. Hence, we aimed to evaluate the therapeutic potential of ivermectin in combination with PTX and investigate the molecular mechanisms by which ivermectin overcomes PTX resistance.</p><p><strong>Materials and methods: </strong>We assessed the antitumor effects of ivermectin in A549 cells treated with or without PTX. We also established PTX-resistant cells using this cell line and explored the underlying mechanisms. Additionally, we evaluated whether ivermectin attenuates PTX-resistance with the retrieval of drug sensitivity.</p><p><strong>Results: </strong>Combined treatment of A549 cells with PTX and ivermectin inhibited cell growth. These cells acquired chemoresistance upon long-term exposure to gradually increasing PTX concentrations, which was accompanied by ABCB1 mRNA up-regulation, and subsequent overproduction of P-glycoprotein (P-gp). Consistent with this, P-gp over-expression resulted in a PTX-resistant phenotype. Notably, the simultaneous ivermectin treatment during the gradual exposure completely abolished P-gp expression, leading to an increased intracellular PTX concentration and sustained PTX sensitivity. Ivermectin was found to regulate P-gp expression via the EGFR/ERK/Akt/NF-[Formula: see text]B pathway.</p><p><strong>Conclusion: </strong>Combined treatment of PTX-resistant A549 cells with ivermectin and PTX may circumvent PTX resistance caused by P-gp induction, highlighting a novel therapeutic avenue for drug repurposing.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5271-5282"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MRTX1719, an MTA-cooperative PRMT5 Inhibitor, Induces Cell Cycle Arrest and Synergizes With Oxaliplatin and Gemcitabine for Enhanced Anticancer Effects.","authors":"Toshihiro Soeta, Norihiko Sugisawa, Akihiro Yamamura, Naoki Tanaka, Hirofumi Imoto, Takahiro Tsuchiya, Takashi Aizawa, Koji Okamoto, Mari Kawamura, Fumito Saijo, Masamichi Mizuma, Shinobu Ohnuma, Takashi Kamei, Michiaki Unno","doi":"10.21873/anticanres.17351","DOIUrl":"https://doi.org/10.21873/anticanres.17351","url":null,"abstract":"<p><strong>Background/aim: </strong>MRTX1719 is a novel protein arginine methyltransferase 5 (PRMT5) inhibitor that targets the PRMT5-5'-Methylthioadenosine (MTA) complex called MTA-cooperative PRMT5 inhibitor. MRTX1719 acts specifically on methylthioadenosine phosphorylase (MTAP)-deficient cancer cells; however, its mechanism of action remains unclear. This study aimed to clarify the effects of MRTX1719 on the cell cycle and its synergistic effects with other anticancer drugs.</p><p><strong>Materials and methods: </strong>A cell cycle assay was conducted using fluorescence-activated cell sorting to examine the correlation between PRMT5 activity and cells in the G<sub>0</sub>/G<sub>1</sub> phase. The synergistic effects of MRTX1719 and anticancer drugs were evaluated using the Combination Index (CI) and Bliss synergy score (BSS). The synergistic effect was also evaluated by knocking down the endogenous expression of MTAP in HCT116 cells with high MTAP expression.</p><p><strong>Results: </strong>The cell cycle assay showed that the population of cells with reduced PRMT5 activity increased, and the administration of MRTX1719, an MTAP inhibitor, increased the population of cells in the G<sub>0</sub>/G<sub>1</sub> phase. In the synergistic effect assay, oxaliplatin and gemcitabine demonstrated a CI <1 and a BSS >0, indicating a synergistic effect when administered alongside MRTX1719. MTAP knockdown also resulted in <1 in CI and >0 in BSS after the administration of oxaliplatin or gemcitabine with MRTX1719.</p><p><strong>Conclusion: </strong>MRTX1719 reduces PRMT5 activity, leading to cell cycle arrest by increasing the proportion of cells in the G<sub>0</sub>/G<sub>1</sub> phase. Moreover, MRTX1719 exhibits synergistic anticancer effects with oxaliplatin and gemcitabine in MTAP-deficient cancer cells.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5231-5240"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic Factors of Flap Complications After Carbon-ion Radiotherapy for Head and Neck Cancer With Reconstruction.","authors":"Hiroaki Ikawa, Masashi Koto, Tokuhiko Omatsu, Shuri Aoki, Hirotoshi Takiyama, Tetsuro Isozaki, Makoto Shinoto, Reiko Imai, Hiroshi Tsuji, Shigeru Yamada","doi":"10.21873/anticanres.17383","DOIUrl":"https://doi.org/10.21873/anticanres.17383","url":null,"abstract":"<p><strong>Background/aim: </strong>The incidence of flap complications after carbon-ion (C-ion) radiotherapy (RT) for head and neck cancer with reconstruction is unknown. This study investigated the incidence and risk factors of flap complications following C-ion RT for head and neck cancer with reconstruction.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 24 cases, excluding cases of re-irradiation, treated with C-ion RT at QST Hospital for loco-regional recurrence after reconstructive surgery for head and neck cancers from April 1997 to March 2020. We evaluated flap complications as anastomosis-related (flap loss and necrosis) and flap bed-related (wound dehiscence) complications. Wound dehiscence was assessed using Common Terminology Criteria for Adverse Events version 5.0. The correlation between clinical factors, dosimetric parameters, and flap complication was analyzed retrospectively.</p><p><strong>Results: </strong>The median follow-up period was 42.2 months (range=6.7-155.9 months). None of the 24 enrolled patients experienced flap loss and flap necrosis, and two (8.3%) patients had grade 1 wound dehiscence; grade 2 or greater toxicities were not recorded. The median interval between C-ion RT and wound dehiscence of the flap was 6.8 (6.5 and 7.0) months. Univariate analysis to identify clinical and dose-volume histogram parameters associated with the occurrence of grade 1 wound dehiscence after C-ion RT revealed that the minimum dose (Dmin) ≥5.9 Gy for flap was a statistically significant risk factor (p=0.017).</p><p><strong>Conclusion: </strong>C-ion RT for head and neck cancers after reconstructive surgery is safe, with no serious flap complications. Dmin was an independent risk factor for the development of wound dehiscence.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5569-5576"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD47 and Calreticulin Expression in Breast Cancer Subtypes and Anti-CD47 Inhibitory Effects in Macrophage-mediated Phagocytosis.","authors":"Juthamard Chantaraamporn, Phattarin Pothipan, Titipatima Sakulterdkiat, Burana Khiankaew, Lalita Lumkul, Photsathorn Mutapat, Phichamon Phetchahwang, Jisnuson Svasti, Voraratt Champattanachai","doi":"10.21873/anticanres.17318","DOIUrl":"10.21873/anticanres.17318","url":null,"abstract":"<p><strong>Background/aim: </strong>Macrophage-mediated cancer immune evasion is modulated by the balance between \"the cluster of differentiation 47 (CD47), an anti-phagocytic signal\" and \"calreticulin (CALR), a pro-phagocytic signal\". CD47 is highly expressed in various types of cancer. However, the expression profiles of CD47 and CALR in breast cancer, especially in different hormone receptor subtypes, and the effects of CD47 blockade in macrophage-mediated therapy are not well understood.</p><p><strong>Materials and methods: </strong>The expression levels of CD47 and CALR were investigated in breast cancer and adjacent normal tissues using immunohistochemistry. To study the effects of CD47 blockade therapy, CD47 and CALR expression in breast cancer cell lines were determined. In vitro macrophage-mediated phagocytosis of breast cancer upon treatment with a monoclonal CD47 antibody (B6H12) were performed.</p><p><strong>Results: </strong>CD47 and CALR were overexpressed in breast cancer tissues and their up-regulation was associated with hormone receptor subtypes. Patients with Luminal A breast cancer had higher levels of CD47, while patients with triple-negative breast cancer (TNBC) had higher levels of CALR. The levels of CD47 and CALR were also elevated in breast cancer cell lines of Luminal A (MCF-7) and TNBC (MDA-MB-231) subtypes. Interestingly, the expression ratio of surface CD47/CALR was significantly higher in MCF-7. Moreover, in vitro phagocytosis assays revealed that blockage of CD47 enhanced macrophage-mediated activity in both cancer cells with dramatically higher degrees of phagocytosis in MCF-7.</p><p><strong>Conclusion: </strong>The expression profiles of CD47 and CALR in breast cancer subtypes and the benefit of CD47 blocking-based immunotherapy are herein provided.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4929-4940"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiyeon Lee, Sang Ah Chi, Sangjoon Choi, Hyun-Soo Kim
{"title":"Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix: Comparison of Its Clinicopathological Characteristics and Programmed Death-ligand 1 Expression Status With Those of Other Endocervical Adenocarcinomas.","authors":"Jiyeon Lee, Sang Ah Chi, Sangjoon Choi, Hyun-Soo Kim","doi":"10.21873/anticanres.17325","DOIUrl":"10.21873/anticanres.17325","url":null,"abstract":"<p><strong>Background/aim: </strong>Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA).</p><p><strong>Patients and methods: </strong>PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity.</p><p><strong>Results: </strong>ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response.</p><p><strong>Conclusion: </strong>All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5007-5022"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of the Predictive and Prognostic Capacities of Neutrophil, Lymphocyte and Platelet Counts and Tumor-infiltrating Lymphocytes in Triple-negative Breast Cancer: Preliminary Results of the PERCEPTION Study.","authors":"Alexia Giro, Judith Passildas-Jahanmohan, Myriam Kossai, Yannick Bidet, Ioana Molnar, Maureen Bernadach, Frederique Penault-Llorca, Catherine Abrial, Xavier Durando, Nina Radosevic-Robin","doi":"10.21873/anticanres.17323","DOIUrl":"https://doi.org/10.21873/anticanres.17323","url":null,"abstract":"<p><strong>Background/aim: </strong>Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype, posing numerous challenges in clinical decision-making. Biomarkers are essential to personalize management of TNBC patients. While tumor infiltrating lymphocytes (TILs) are validated prognostic biomarkers, the requirement for tumor biopsy limits their routine use. Therefore, more accessible and reliable quantitative biomarkers are needed. Given the significant role of systemic inflammatory response in tumor onset and progression, assessing inflammatory cells via liquid biopsies emerges as a promising alternative.</p><p><strong>Patients and methods: </strong>The PERCEPTION study, conducted at Centre Jean Perrin in France, aims to determine the correlation between TILs and peripheral blood components at diagnosis. An interim analysis was conducted after enrolling 50% of the estimated population, to evaluate study feasibility and preliminary correlations between blood cell counts and TILs.</p><p><strong>Results: </strong>Sixty-one patients were enrolled over 4.5 years, demonstrating a good inclusion rate with minimal missing data. Preliminary results for 36 analyzable patients showed no correlation between the neutrophil-to-lymphocyte ratio (NLR) and TILs (r<sub>s</sub>=-0.19, 95%CI=-0.49-0.16, p=0.3). However, a moderate, positive, statistically significant correlation was found between NLR and the CD8/FoxP3 TILs ratio (r<sub>s</sub>=0.36, 95%CI=0.03-0.64, p=0.043). The probabilistic index of 0.7 (p=0.06) between NLR-high and NLR-low groups for this ratio supports the correlation.</p><p><strong>Conclusion: </strong>The interim analysis of the PERCEPTION study confirms the feasibility of correlating blood cell counts with TILs in TNBC. Although no significant correlation was observed between NLR and TILs, the moderate positive correlation between the CD8/FoxP3 ratio and TILs suggests a potential link between systemic inflammation and local immune response. These findings underscore the potential of blood-based markers as non-invasive surrogates for TILs, encouraging further research to enhance prognosis and guide treatment strategies in TNBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4983-4994"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alizée Zadoroznyj, Elias Karam, Nicolas Michot, Julien Thiery, Thiery Lecomte, Driffa Moussata, Sophie Chapet, Gilles Calais, Ephrem Salame, Urs Pabst-Giger, Mehdi Ouaissi
{"title":"Clinical and Oncological Impact of a Protective Ileostomy in Rectal Cancer Patients Undergoing Adjuvant Chemotherapy.","authors":"Alizée Zadoroznyj, Elias Karam, Nicolas Michot, Julien Thiery, Thiery Lecomte, Driffa Moussata, Sophie Chapet, Gilles Calais, Ephrem Salame, Urs Pabst-Giger, Mehdi Ouaissi","doi":"10.21873/anticanres.17324","DOIUrl":"https://doi.org/10.21873/anticanres.17324","url":null,"abstract":"<p><strong>Background/aim: </strong>During low anterior rectal resection for rectal cancer, a protective ileostomy (PI) is routinely created to reduce the severity of anastomotic complications. The aim of this study was to investigate the side-effects of PI during adjuvant chemotherapy.</p><p><strong>Patients and methods: </strong>A retrospective cohort of patients was operated on for non-metastatic rectal cancer with a PI during 2005-2022. Patients treated with adjuvant chemotherapy (AC) were compared with those not receiving AC. A subgroup analysis compared patients with early PI closure (<10 weeks) and those with a PI in place during chemotherapy.</p><p><strong>Results: </strong>A total of 242 patients were included: 178 (73.6%) without adjuvant chemotherapy and 64 (26.4%) with. History, tumour location, neoadjuvant treatment and postoperative follow-up were similar for both groups. Patients treated with AC had a greater risk of renal failure (37.5% vs. 14.6%, p=0.0002), ionic disorders (45.3% vs. 26.9% p=0.008), malnutrition (23.4% vs. 5.6%, p=0.0002) and rehospitalization (35.9% vs. 18.5% p=0.007). Patients treated with AC needed significant dose adjustments of oxaliplatin in 40.6% of cases, this adjustment being higher in patients with a PI compared to patients with early closure (47.1 vs. 9.1%, p=0.021).</p><p><strong>Conclusion: </strong>Presence of a PI during chemotherapy predisposes to increased episodes of renal failure, and requires major adaptation of chemotherapy doses, especially of oxaliplatin.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4995-5005"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}