Anna Crispo, Assunta Luongo, Davide Nocerino, Marco Cascella, Marco Crisci, Francesca Bifulco, Daniela Schiavo, Maurizio Marchesini, Sergio Coluccia, Melania Prete, Alfonso Amore, Egidio Celentano, Sabrina Bimonte, Arturo Cuomo
{"title":"Assessment of Breakthrough Cancer Pain Among Female Patients With Cancer: Knowledge, Management and Characterization in the IOPS-MS Study.","authors":"Anna Crispo, Assunta Luongo, Davide Nocerino, Marco Cascella, Marco Crisci, Francesca Bifulco, Daniela Schiavo, Maurizio Marchesini, Sergio Coluccia, Melania Prete, Alfonso Amore, Egidio Celentano, Sabrina Bimonte, Arturo Cuomo","doi":"10.21873/anticanres.17678","DOIUrl":"10.21873/anticanres.17678","url":null,"abstract":"<p><strong>Background/aim: </strong>Chronic secondary pain from cancer may flare into unexpected acute phases, called breakthrough cancer pain (BTcP). This phenomenon has a moderate-to-severe intensity and short latency between onset and peak of intensity, so clinical and therapeutic implications may be necessary. The Italian Oncologic Pain Multisetting-Multicentric Survey (IOPS-MS) aimed to characterize BTcP in a large number of patients from different settings and assess possible factors influencing its development. Previously, we observed differences according to sex in site, onset and level of BTcP. In this analysis, we assessed differences in non-predictable BTcP between female patients with female-specific cancer (FSC) (including breast and gynecological cancer) and those with non-FSC.</p><p><strong>Patients and methods: </strong>A univariate analysis compared patients with FSC (overall and separately for breast and gynecological cancer) and non-FSC. A multivariate analysis stratified by BTcP phenotype was performed to estimate the main determinants of the risk groups in patients with FSC (overall and separately for breast and gynecological cancer) and non-FSC. Odds ratios and 95% confidence intervals were reported.</p><p><strong>Results: </strong>The FSC group was younger, more often treated in clinics or day hospitals, and had an increased risk of locoregional/metastatic disease than the non-FSC group. Patients with breast cancer were at higher risk of locoregional/metastatic disease, less frequently treated by a palliative specialist and had later BTcP onset compared to the non-FSC group. Significant differences concerning age, care setting and BTcP onset were also found in the group of patients with FSC (overall and separately for breast and gynecological cancer) according to tumor extension.</p><p><strong>Conclusion: </strong>Non-predictable BTcP in patients with FSC presents unique characteristics, particularly regarding pain onset, care settings, and metastasis. Differences between breast and gynecological cancer emphasize the need for tailored pain-management approaches.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"3149-3164"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511431","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}
Mark T J VAN Bussel, Nathalie Bravenboer, Huib VAN Essen, Petur Snaebjornsson, Natasha M Appelman-Dijkstra, Jan Hm Schellens, Frans L Opdam
{"title":"Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial.","authors":"Mark T J VAN Bussel, Nathalie Bravenboer, Huib VAN Essen, Petur Snaebjornsson, Natasha M Appelman-Dijkstra, Jan Hm Schellens, Frans L Opdam","doi":"10.21873/anticanres.17677","DOIUrl":"10.21873/anticanres.17677","url":null,"abstract":"<p><strong>Background/aim: </strong>More than 90% of colorectal cancers (CRC) have alterations in WNT signaling. Eight to ten percent of patients with metastatic Kirsten rat sarcoma virus - wild type (KRAS-WT) CRC have B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) mutations and do not benefit from epidermal growth factor receptor (EGFR) antibodies. The addition of a porcupine inhibitor could increase the response rate in patients with BRAFV600E-mutated KRAS-WT metastatic CRC (mCRC) with WNT pathway alterations.</p><p><strong>Patients and methods: </strong>We report two cases of severe bone toxicities during treatment with the BRAF inhibitor encorafenib, the EGFR-targeting monoclonal antibody cetuximab, and the porcupine inhibitor WNT974 in the phase 1B study NCT02278133.</p><p><strong>Results: </strong>Patient 1, a 66-year-old man with BRAFV600E-mutated KRAS-WT mCRC and an RNF43 mutation, developed multiple rib fractures and collapse of thoracic vertebrae 10 and 11. Autopsy revealed no metastases at fracture sites; histology demonstrated a thin, porous cortex and poor trabecular bone structure. Immunohistochemistry assessed key WNT pathway components. Patient 2, a 70-year-old man with similar mutations, experienced a toe fracture, multiple rib fractures, osteopenia, and altered bone biomarkers indicative of disrupted bone turnover.</p><p><strong>Conclusion: </strong>The two patients described developed severe bone toxicities including rib fractures, a toe fracture, osteoporotic thoracic collapses, hypercalcemia, and alternated bone biomarkers. These cases highlight the potential skeletal risks associated with dual MAPK and WNT pathway inhibition.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"3137-3147"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511433","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}
Minh Dung Nguyen, Olena Gorobets, Yannick Joel Djoua, Johan Rose-Dite-Modestine, Vincent Vinh-Hung, Claire Verschraegen, Nam P Nguyen
{"title":"End-of-life Androgen Deprivation Syndrome With Enzalutamide in Metastatic Prostate Cancer: A Case Report.","authors":"Minh Dung Nguyen, Olena Gorobets, Yannick Joel Djoua, Johan Rose-Dite-Modestine, Vincent Vinh-Hung, Claire Verschraegen, Nam P Nguyen","doi":"10.21873/anticanres.17625","DOIUrl":"10.21873/anticanres.17625","url":null,"abstract":"<p><strong>Background/aim: </strong>Enzalutamide is a highly effective anti-androgen for the treatment of prostate cancer. Therapy can incur unbearable fatigue in elderly patients, which might require a reduced dosage. However, the value of reduced-dose treatment to improve the long-term tolerability and to decrease the risk of toxicity remains unknown.</p><p><strong>Case report: </strong>We present the six-year clinical course of a patient treated upfront with low-dose enzalutamide (25% of the standard dose). Despite initial disease control and tolerance, the patient developed progressive frailty and signs of severe androgen deprivation near end-of-life.</p><p><strong>Conclusion: </strong>This case illustrates that while low-dose enzalutamide can provide durable disease control in elderly patients with metastatic castration-resistant prostate cancer, it does not fully prevent the late-onset toxicities associated with androgen deprivation. Personalized treatment strategies - including dose adjustment over time and consideration of intermittent therapy - may help to balance efficacy with quality of life.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2535-2538"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155944","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":"Randomized Study of Short-time Continuous Saline Irrigation After Transurethral Resection in Non-muscle Invasive Bladder Cancer.","authors":"Takehisa Onishi, Sho Sekito, Takuji Shibahara, Tadashi Yabana","doi":"10.21873/anticanres.17636","DOIUrl":"10.21873/anticanres.17636","url":null,"abstract":"<p><strong>Background/aim: </strong>To investigate the efficacy and safety of short-time continuous saline bladder irrigation (S-CSBI) compared to long-time CSBI (L-CSBI) after transurethral resection of bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC).</p><p><strong>Patients and methods: </strong>Between 2016 and 2021, 323 patients with suspected primary NMIBC based on cystoscopic appearance were enrolled. Patients were randomly allocated to receive S-CSBI (3 hours) or L-CSBI (overnight) after TURBT. Patients with the highest risk NMIBC and muscle-invasive bladder cancer were excluded. The primary endpoint was the 2-year recurrence-free survival (RFS) rate for S-CSBI, which was tested for non-inferiority. A difference of 15% in the 2-year RFS rate (60%) was defined as the non-inferiority margin for comparing the long-time CSBI.</p><p><strong>Results: </strong>A total of 230 patients (110 in the S-CSBI group and 120 in the L-CSBI group) remained for the per-protocol analysis after exclusion. The 2-year RFS rates for S-CSBI and L-CSBI were 70.5% [95% confidence interval (CI)=60.9-78.2] and 70.5% (95%CI=61.4-77.9), respectively. The 95%CI for S-CSBI was above the lower non-inferiority limit of 60%, confirming the non-inferiority of S-CSBI to L-CSBI. The intention to treat analysis also demonstrated the non-inferiority of S-CSBI. In terms of adverse events, no severe systemic toxicities were observed in either group, hematuria grade IIIa was higher in the S-CSBI group, although not statistically significant.</p><p><strong>Conclusion: </strong>S-CSBI after TURBT was non-inferior to L-CSBI with regard to the 2-year RFS rate. S-CSBI is easy to administer, especially in day surgery, and may be a treatment choice for patients with NMIBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2653-2660"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155621","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":"Efficacy and Treatment Outcomes of First-line Pazopanib Therapy in Advanced Renal Cell Carcinoma in Greece.","authors":"Evangelos Bournakis, Ioannis Xanthakis, Michail Vaslamatzis, Parisis Makrantonakis, Charisios Karanikiotis, Ilias Athanasiadis, Alexandros Ardavanis, Pavlos Papakotoulas, Epaminondas Samantas, Christos Papandreou, Maria Michailidou, Panagiotis Katsaounis, Christos Christodoulou","doi":"10.21873/anticanres.17624","DOIUrl":"10.21873/anticanres.17624","url":null,"abstract":"<p><strong>Background/aim: </strong>Pazopanib is a tyrosine kinase inhibitor (TKI) approved as first-line treatment for renal cell carcinoma (RCC). Although pazopanib efficacy and safety have been established in phase III studies, real-world data are limited. The aim of this study was to evaluate pazopanib efficacy, duration of responses and safety, as first-line treatment in patients with advanced/metastatic RCC with favorable-intermediate prognosis.</p><p><strong>Patients and methods: </strong>This single-arm prospective Greek observational study evaluated 59 patients treated with first-line pazopanib as indicated, and who were followed-up every 3 months for 2 years, or until disease progression. The primary objective was to evaluate the efficacy of first-line pazopanib treatment in patients with favorable-intermediate prognosis metastatic RCC at 9 months from treatment onset.</p><p><strong>Results: </strong>The primary composite efficacy point (complete response, partial response, or stable disease at 9 months) was reached by 30.5% [95% confidence interval (CI)=19.2-43.9%] of patients, with 27.1% (95% CI=16.4-40.3%) of patients demonstrating stable disease. Best overall response was complete response in 5.1% (3/59 patients), partial response in 22% (13/59 patients), and stable disease in 35.6% (21/59 patients). Median progression-free survival was 17.7 (95% CI=9.15-26.25) months and declined with the International Metastatic Renal Cell Carcinoma Database Consortium progressive risk (24.5 and 6.97 months for favorable- and intermediate-risk, respectively; <i>p</i>=0.012). The cumulative overall survival rate was 95% after 9 (95% CI=89.8-100.0%) months and 24 (95% CI=89.8-100.0%) months. Median overall survival was not reached. Overall, 234 adverse events were reported in 55 patients, of which the most common were malignant neoplasm progression, diarrhea, and hypertension.</p><p><strong>Conclusion: </strong>These data demonstrate that pazopanib is well-tolerated and effective as first-line treatment in patients with favorable-intermediate risk metastatic RCC in real-life conditions in Greece.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2527-2534"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155912","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}
Vincenzo Iorio, Pietro Delia, Angela Pia Solazzo, Ivan Fazio, Antonino Daidone, Andrea Girlando, Nicola DE Rosa, Alfio DI Grazia, Annalisa LA Macchia, Santa Bambace, Salvatore Parisi, Cesare Guida, Matteo Muto, Vincenzo Carfora, Mariangela Boccardi, Salvatore Bonanno, Francesca Doria, Alfonsina Pepe, Giuseppe Iatì, Antonio Spera, Gianluca Mortellaro, Alessandro Fanelli, Vincenzo Barone, Paolo Muto, Maria Rosaria Valerio, Giuseppa Scandurra, Daniela Sambataro, Grazia Lazzari, Maria Enfasi, Vittorio Gebbia
{"title":"Phase II Study of the Effectiveness of the Germinated Wheat-derived Rigenase Plus Polyhexanide in the Prophylaxis for Hypofractionated Radiation-induced Acute Skin Toxicity in Breast Cancer.","authors":"Vincenzo Iorio, Pietro Delia, Angela Pia Solazzo, Ivan Fazio, Antonino Daidone, Andrea Girlando, Nicola DE Rosa, Alfio DI Grazia, Annalisa LA Macchia, Santa Bambace, Salvatore Parisi, Cesare Guida, Matteo Muto, Vincenzo Carfora, Mariangela Boccardi, Salvatore Bonanno, Francesca Doria, Alfonsina Pepe, Giuseppe Iatì, Antonio Spera, Gianluca Mortellaro, Alessandro Fanelli, Vincenzo Barone, Paolo Muto, Maria Rosaria Valerio, Giuseppa Scandurra, Daniela Sambataro, Grazia Lazzari, Maria Enfasi, Vittorio Gebbia","doi":"10.21873/anticanres.17626","DOIUrl":"10.21873/anticanres.17626","url":null,"abstract":"<p><strong>Background/aim: </strong>To assess the efficacy of the wheat extract rigenase plus the antiseptic polyhexanide spray in preventing and reducing the incidence of grade 2-3 acute radiation-induced skin toxicity (RIST) in patients undergoing adjuvant hypo-fractionated radiotherapy to the breast for cancer.</p><p><strong>Patients and methods: </strong>Three hundred and twenty-four patients participated in this study, enrolled in 15 centers in Southern Italy. Rigenase/polyhexanide was applied twice a day, starting on the first day and ending two weeks post-radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy and at 2-4 weeks after treatment. Outcome measures were assessed using the Common Toxicity Criteria of the National Cancer Institute RIST criteria.</p><p><strong>Results: </strong>In most cases, RIST was observed after three weeks of radiotherapy. Grade 2 skin toxicity was recorded in 24% of patients, starting from week 2 with a peak at week 3. Grade 3 was observed starting from week 2 with a peak at week 3 where it was recorded in 4.5% of patients. The incidence of grade 2 and 3 progressively declined and disappeared by week 8. The median perceived benefit among patients and treating physicians differed significantly. All patients well tolerated treatment with rigenase/polyhexanide without meaningful side-effects. Twenty-one patients (0.06%) complained of light pruritus and two stopped rigenase/polyhexanide after 1 and 2 weeks.</p><p><strong>Conclusion: </strong>Patients treated with adjuvant hypo-fractionated radiotherapy for breast cancer developed grade 2 RIST in slightly less than a quarter of cases with the use of rigenase/polyhexanide. No treatment delays or withdrawals were observed because of RIST. The tolerance was excellent.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2539-2550"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156026","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}
Sa Deok Hong, Min Sil Kang, Nar Bahadur Katuwal, Mithun Ghosh, Nahee Park, Young Bin Cho, Kamal Pandey, Ah-Young Kown, Hee Jung Ahn, Seul-Gi Kim, Young Seok Baek, In Jee Lee, Seung Ryeol Lee, Yong Wha Moon
{"title":"Intratumoral Injection of Allogeneic NK Cell With Chemotherapy in a Triple-negative Breast Cancer Preclinical Model.","authors":"Sa Deok Hong, Min Sil Kang, Nar Bahadur Katuwal, Mithun Ghosh, Nahee Park, Young Bin Cho, Kamal Pandey, Ah-Young Kown, Hee Jung Ahn, Seul-Gi Kim, Young Seok Baek, In Jee Lee, Seung Ryeol Lee, Yong Wha Moon","doi":"10.21873/anticanres.17638","DOIUrl":"10.21873/anticanres.17638","url":null,"abstract":"<p><strong>Background/aim: </strong>Conventional therapies for triple-negative breast cancer (TNBC) usually exhibit low efficacy. This study aimed to demonstrate the feasibility and antitumor efficacy of intratumoral (IT) injection of allogeneic natural killer (NK) cells with or without chemotherapy in the TNBC preclinical model.</p><p><strong>Materials and methods: </strong>The TNBC preclinical models were generated in athymic nude and NOD/SCID mice. We assessed NK cell biodistribution and efficacy through bioimaging, immunohistochemistry, TUNEL assay and tumor growth pattern following peritumoral (PT), intravenous (IV) and IT injections. The <i>in vitro</i> anticancer effects of NK cells combined with chemotherapy (paclitaxel and carboplatin) were evaluated using MTS, qRT-PCR, and FACS analysis. <i>In vivo</i> anticancer effect was analyzed by tumor growth patterns and TUNEL assay.</p><p><strong>Results: </strong>IT injection of NK cells resulted in superior tumor infiltration, apoptosis induction, and localized accumulation compared to PT and IV routes. Despite using only 10% of the NK cell dose used for IV administration, IT injection achieved comparable tumor growth suppression. Furthermore, combining IT NK cell therapy with chemotherapy produced additive effects, enhancing both tumor growth inhibition and apoptosis. Chemotherapy was found to upregulate the expression of NKG2D ligands at both mRNA and protein levels on cancer cells, potentially increasing their susceptibility to NK cell-mediated cytotoxicity.</p><p><strong>Conclusion: </strong>IT injection of NK cells was feasible and added anticancer efficacy to systemic chemotherapy in TNBC preclinical models. Therefore, this study supports the rationale of further clinical development of IT NK therapy with or without chemotherapy in patients with TNBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2669-2688"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155981","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}
Jack D Sleeman, Jessica Delgado, Danny Sleeman, Marina M Tabbara, Gaetano Ciancio
{"title":"Liposarcomas of the Kidney and Surgical Management.","authors":"Jack D Sleeman, Jessica Delgado, Danny Sleeman, Marina M Tabbara, Gaetano Ciancio","doi":"10.21873/anticanres.17617","DOIUrl":"10.21873/anticanres.17617","url":null,"abstract":"<p><strong>Background/aim: </strong>Retroperitoneal liposarcomas of the kidney are rare malignancies with a poor prognosis due to a high recurrence rate and their ability to spread in the retroperitoneum before causing any noticeable symptoms. Because these tumors are so rare and their surgical removal can be complicated by the involvement of many organs and vessels inside the abdomen, there is a need for more documentation on the procedures by which surgeons remove these tumors.</p><p><strong>Patients and methods: </strong>In this article, we describe a case series of four patients presenting with retroperitoneal liposarcomas that required surgical resection of the tumor along with radical nephrectomies. Some of these cases benefitted from liver mobilization similar to that performed during liver transplantation, in order to more clearly identify the entire scope of these large retroperitoneal tumors. Here, we demonstrate unique ways of managing such patients with these rare tumors.</p><p><strong>Results: </strong>The operative times for patients 1, 2, 3, and 4 were 240, 249, 167, and 272 minutes, respectively. Estimated blood loss ranged from 250 to 2,000 cc, with only patients 1 and 4 requiring blood transfusions. Postoperative complications included bile leakage in patient 1 and prolonged ileus in patient 4, which resolved without further intervention.</p><p><strong>Conclusion: </strong>Our case series underscores the importance of comprehensive surgical management in patients with large, locally advanced renal liposarcomas. Moreover, development of carefully selected individualized treatment plans including adjuvant therapy when appropriate, is critical to improve long-term survival outcomes for patients with renal liposarcoma.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 6","pages":"2459-2465"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155954","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}
Jinsoo Kim, Qinghong Han, Byung Mo Kang, Kohei Mizuta, Yohei Asano, Michael Bouvet, Robert M Hoffman
{"title":"Combination of Recombinant Methioninase With Rapamycin or Chloroquine Is Synergistic to Highly Inhibit Triple-negative Breast Cancer Cells <i>In Vitro</i>.","authors":"Jinsoo Kim, Qinghong Han, Byung Mo Kang, Kohei Mizuta, Yohei Asano, Michael Bouvet, Robert M Hoffman","doi":"10.21873/anticanres.17564","DOIUrl":"https://doi.org/10.21873/anticanres.17564","url":null,"abstract":"<p><strong>Background/aim: </strong>Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer with a poor prognosis despite multimodal treatment. New therapeutic approaches for TNBC are necessary. We very recently showed that the triple combination of recombinant methioninase (rMETase), rapamycin (RAPA), and chloroquine (CQ) synergically eradicated osteosarcoma cells <i>in vitro</i>. The present study aimed to determine whether rMETase has synergistic efficacy with either RAPA or CQ on a TNBC cell line.</p><p><strong>Materials and methods: </strong>The half-maximal inhibitory concentrations (IC<sub>50</sub>) of rMETase, RAPA, and CQ were determined on the human MDA-MB-231 TNBC cell line <i>in vitro</i>. The efficacy of rMETase, combined with RAPA or with CQ, at their respective IC<sub>50</sub> values, on MDA-MB-231 cell viability was determined using the WST-8 assay.</p><p><strong>Results: </strong>The IC<sub>50</sub> of rMETase was 0.56 U/ml, for RAPA the IC<sub>50</sub> was 3.9 μM, and for CQ the IC<sub>50</sub> was 5.0 μM. The viability of the MDA-MB-231 cells was significantly decreased after treatment with rMETase plus RAPA or rMETase plus CQ, compared to the control cells or cells treated with one drug only.</p><p><strong>Conclusion: </strong>rMETase, when combined with either RAPA or CQ, is synergistic on the MDA-MB-231 TNBC cell line. The present findings suggest the potential for future clinical applications of rMETase plus chemotherapy, such as RAPA or CQ, for recalcitrant TNBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1853-1859"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974027","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}
Jonathan Keul, Swetlana Sperling, Veit Rohde, Milena Ninkovic
{"title":"Advantages and Disadvantages of Drug Combination Treatment: Riluzole, Metformin and Dexamethasone Effect on Glioblastoma Cell.","authors":"Jonathan Keul, Swetlana Sperling, Veit Rohde, Milena Ninkovic","doi":"10.21873/anticanres.17561","DOIUrl":"https://doi.org/10.21873/anticanres.17561","url":null,"abstract":"<p><strong>Background/aim: </strong>In glioblastoma multiforme (GBM), a deadly brain tumor, glucose is one of the main fuels for accelerated growth. Patients with GBM are also exposed to excess glucose through hyperglycemia in diabetes mellitus. In addition, dexamethasone (Dex), a corticosteroid commonly administered for controlling cerebral oedema, causes additional excess glucose. Therefore, targeting glucose metabolism is an attractive therapeutic intervention for GBM treatment. We have recently shown that riluzole (Ril), a drug used to treat amyotrophic lateral sclerosis (ALS), has an effect on some detrimental Dex-induced metabolic changes in GBM. Therefore, we examined the effect of the combination of metformin (Met), widely used to treat type 2 diabetes, and Ril on GBM cells.</p><p><strong>Materials and methods: </strong>The 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability of U87MG after treatment with Ril, Met, Ril plus Met (Ril+Met) and the addition of Dex to this co-treatment. Cell migration was assessed by the xCELLigence system, matrix metalloproteinase 2 (MMP2) activation by zymography assay and gene expression by real-time polymerase chain reaction (RT-PCR).</p><p><strong>Results: </strong>Co-treatment with Ril and Met was effective in killing GBM cells and reducing the expression of genes involved in glucose and stem cell metabolism. Furthermore, combination of Ril and Met reduced MMP2 activation. But co-administration increased the migration of U87MG cells. The addition of Dex to this combination reversed the unfavorable effects of Ril+Met on cell migration.</p><p><strong>Conclusion: </strong>Ril+Met co-treatment had a positive effect in terms of GBM cell death, decreased expression of genes involved in glucose metabolism and stemness, and reduced MMP2 activation. Disadvantage of Ril+Met treatment was increased cell migration. Taken together, these drug combinations may also allow the reduction of the concentration of Dex to minimize its side effects.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1813-1823"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970285","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}