Cisplatin Therapy Research Articles

Predictive ability of the geriatric 8 screening tool for treatment completion of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin therapy in patients with urothelial carcinoma.

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) therapy is expected to provide superior therapeutic efficacy compared to gemcitabine and cisplatin therapy as systemic chemotherapy for urothelial carcinoma. However, its high incidence of adverse events raises concerns about tolerability, particularly in older patients. This study evaluated the utility of the Geriatric 8 (G8) screening tool in patients undergoing dd-MVAC therapy and assessed its association with treatment progress. A retrospective analysis was conducted on 65 patients with urothelial carcinoma who received dd-MVAC therapy between August 2018 and May 2023, with the goal of completing six treatment cycles. The G8 score was evaluated before treatment initiation, and its association with treatment completion and adverse events was examined. The median age of patients was 71 years (range, 43-84 years), with 65% male and 35% female. The median pretreatment G8 score was 13 (range, 7-17). Patients with a G8 score ≥14 demonstrated a significantly higher six-cycle treatment completion rate than those with a G8 score <14 (87% vs. 60%, P = 0.026). The incidence of adverse events did not differ between the groups. Furthermore, among various clinicopathological factors, the G8 score was identified as an independent predictor of six-cycle treatment completion (odds ratio: 0.17, P = 0.021), along with Eastern Cooperative Oncology Group Performance Status. Pretreatment G8 scores were associated with the treatment completion rates of dd-MVAC therapy.

Guardian Ion: Intravenous Magnesium as a Nephroprotective Ally in Cisplatin Therapy

Guardian Ion: Intravenous Magnesium as a Nephroprotective Ally in Cisplatin Therapy

Association of KRAS variants with survival and therapeutic outcomes in biliary tract cancers

Association of KRAS variants with survival and therapeutic outcomes in biliary tract cancers

PIKfyve inhibition induces antitumor immunogenicity by attenuating STING trafficking and lysosomal degradation.

Significant progress in the application of immune checkpoint blockade (ICB) for the treatment of multiple types of cancers has been achieved, but its overall response rate and therapeutic efficacy remain unsatisfactory. To address these limitations, the identification of a combinational approach to enhance the therapeutic efficacy of ICB is needed. The activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling is critical to the induction of antitumor innate immune responses and is a promising target for the development of combinational immunotherapy. Here, through the Connectivity Map database and a kinase inhibitor library screen using interferon-stimulated genes (ISGs) as a functional readout, we identified PIKfyve as a negative regulator of cGAS-STING signaling. The inhibition of PIKfyve by the kinase inhibitor YM201636, or genetic ablation elicited the expression of ISGs downstream of cGAS-STING and reshapes the antitumor microenvironment by recruiting CD8+ T lymphocytes. In melanoma models, PIKfyve inhibition conferred sensitivity to the combinational therapy of cisplatin and anti-PD1, which lead to a durable treatment response. Depletion of Sting or CD8+ T cells in B16F10 tumor significantly weakened the synergistic effect of PIKfyve inhibition and cisplatin. Mechanistically, PIKfyve interacts with STING to facilitate its trafficking from endosome to lysosome for degradation, thereby suppressing the STING-signaling mediated antitumor activity. These results highlight the importance of maintaining STING signaling as a direction to augment the efficacies of combinational immunotherapies.

Micronized Purified Flavonoid Fraction (Diosmin/Hesperidin) Ameliorates Cardiac Structural and Functional Integrity in Cisplatin-treated Male Wistar Rats by Modulating NLRP3/Caspase-1/-3 Signaling.

Cisplatin is an effective chemotherapeutic agent in managing several cancers. Yet, its usage is restricted by its toxicity to non-target organs, such as cardiotoxicity that is mediated by nucleotide-binding Oligomerisation Domain (NOD)-Like Receptors family pyrin domain containing 3 (NLRP3)-driven inflammation, oxidative stress, and apoptosis. Conversely, micronized purified flavonoid fractions (MPFF) attenuate oxido-inflammation by downregulating NLRP3 inflammasome. However, there is a dearth of information on the effect of MPFF on cisplatin-induced cardiac injury. This study examined the possible protective effect of MPFF in cisplatin-induced cardiac injury. Also, the role of NLRP3 inflammasome and caspase-1/-3 signaling was evaluated. Thirty-two adult male Wistar rats were randomly allotted to four equal groups (n = 8 rats per group). The control received 0.5 mL of distilled water orally daily, the MPFF-treated rats received 100 mg/kg/day of MPFF orally for 14 days, the cisplatin-treated rats had 7 mg/kg of cisplatin via an intraperitoneal route on day 8, and the cisplatin+MPFF -treated rats received cisplatin and MPFF as those in the cisplatin- and MPFF-treated groups. Cisplatin therapy significantly increased cardiac injury markers and plasma glucose. Cisplatin also induced dyslipidemia and insulin resistance. Moreover, cisplatin altered cardiac histology evidenced by vascular congestion, and increased myofibril thickness and interstitial space. These observations were accompanied by cisplatin-induced cardiac oxidative stress (increased malondialdehyde and a decline in reduced glutathione, superoxide dismutase, and catalase), inflammation (increased tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6), apoptosis (increased caspase 1 and caspase 3) and a marked increase in NLPR3 inflammasome. These derangements were blunted by MPFF co-therapy. In conclusion, this study for the first time demonstrated that MPFF attenuated cisplatin-induced cardiac structural and functional damage by suppressing oxidative stress and inflammation via the downregulation of NLPR3 /caspase-1/-3 signaling.

Long-term survival with complete remission after irinotecan plus cisplatin therapy for metachronous liver metastasis from a gastric mixed neuroendocrine-non-neuroendocrine neoplasm: a case report.

Gastric mixed neuroendocrine-non-neuroendocrine neoplasm, which consists of both exocrine and endocrine components, is rare and exhibits aggressive biological behavior and poor prognosis. A 64-year-old man underwent investigation for abdominal pain. An endoscopic examination revealed a 30-mm protruded lesion in the gastric antrum for which distal gastrectomy with lymph node dissection was performed. Histopathological examination showed two distinct components, an adenocarcinoma component and neuroendocrine carcinoma component, with immunohistochemical staining positive for CD56, chromogranin A, and synaptophysin. The final diagnosis was mixed neuroendocrine-non-neuroendocrine neoplasm, pT2, pN3, M0, stage IIIA. Multiple liver metastases were detected 3months after surgery. The patient received irinotecan plus cisplatin therapy, which was effective, and the liver metastases disappeared. The patient remains alive, without any recurrence, more than 10years after surgery. We present a rare case of gastric mixed neuroendocrine-non-neuroendocrine neoplasm and review the literature to contribute to improving our understanding of this kind of tumor.

Conversion Surgery Performed Following Durvalumab Combined With Gemcitabine and Cisplatin in Cholangiocarcinoma: A Case Report

Background/AimImmunotherapy using immune checkpoint inhibitors (ICIs) has been widely approved for many cancers. ICI therapy has also been performed for unresectable bile duct cancer in recent years. However, there are few reports of conversion surgery following ICI therapy for unresectable or borderline resectable bile duct cancer. Herein, we present a case of conversion surgery following immune checkpoint ICI therapy for unresectable cholangiocarcinoma, focusing on the cancer immune microenvironment of this case.Case ReportA 77-year-old man was diagnosed with borderline resectable, distal bile duct cancer and hilar cholangiocarcinoma. The patient underwent four courses of durvalumab combined with gemcitabine and cisplatin (Dur+GC) therapy. Evaluation of disease progression showed stable disease (SD), and considering the patient’s surgical risk, a pancreaticoduodenectomy was performed. Adenocarcinoma components remained, and detailed pathological examinations using immunohistochemistry were performed. Marked infiltration of lymphocytes was observed in both the cancer core area and the margin area. The lymphocytes were positive for CD3 and CD8, with a subset also expressing CD103. PD-L1 expression was weakly positive in the stromal area, and positive cells were likely to be infiltrating macrophages in morphological features. Cancer cells were positive for HLA-A/B/C and beta-2.ConclusionCD103+ CD8+ T cells, recently referred to as tissue-resident memory T cells, might be a critical immune cell population involved in ICI-induced anticancer immune responses in cholangiocarcinoma.

Abstract LB172: Chemoradiation-induced tissue toxicity in oral cancer using 3D Epithelioids

Abstract Background: Oral mucositis is among the most prevalent side effects of head and neck cancer (HNC) therapy, impacting over 40% of patients treated with chemotherapy and 90% of those treated with chemoradiation. This widespread inflammation of the oral mucosa represents a major obstacle to the treatment and quality of life of HNC patients and is often a precursor of subsequent oral complications like dysphagia and infections. Although progress has been made in deciphering the mechanisms of oral mucositis, models to study this chemoradiotoxicity have been largely limited to tumor-bearing in vivo models which are both time and cost intensive. To overcome this, the Antoran lab has developed epithelioids, a novel in vitro system that recapitulates 3D epithelial structures from mouse and human tissues and can be extended to cancer epithelioids which recapitulate interactions between healthy and tumor cells along with the tumor microenvironment. Methods: The tongue and oral mucosa were excised from euthanized mice and the muscle layers were removed with forceps. Epithelium from both tissues was cut into small explants, plated on transparent six-well pored membrane trans wells, and incubated with keratinocyte typical media. Squamous cell carcinoma cells of varying aggressiveness were added in the center of each insert. Once confluent, the oral cancer epithelioids were treated with cisplatin, x-ray radiation, or both. Normal and tumor cell viability, proliferation, and recovery was observed using spinning disk confocal live imaging and immunofluorescent staining. Results &amp; Discussion: Real-time live-cell imaging confirmed epithelial cell growth to confluency followed by tumor invasion. Following cisplatin, x-ray irradiation, or combination therapy, epithelioids showed increased markers of DNA-damage and repair such as yH2AX and 53BP1 respectively, apoptosis, and decreased epithelial barrier function as measured by dextran-FITC permeability assays. Relative to normal tissue in the cancer epithelioids, cancer tissue showed greater double-stranded DNA damage in response to chemoradiation. Conclusion: Our results suggest that cancer epithelioids are a promising in vitro alternative to more complex in vivo models and may be used for studying mechanisms of oral mucositis and potential therapeutic interventions of this side effect. Citation Format: George Morcos, Erini Terpsi Vitti, Ines Ferreira, Philippa Samella, David Fernandez-Antoran. Chemoradiation-induced tissue toxicity in oral cancer using 3D Epithelioids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB172.

Abstract 7218: Preventive use of trilaciclib in Chinese patient with extensive-stage small cell lung cancer (ES-SCLC) receiving chemotherapy: A multi-center, single-arm, observational real-world study

Abstract Background: Extensive-stage small cell lung cancer (ES-SCLC) is a highly aggressive disease characterized by rapid progression and development of extensive metastases. Standard chemotherapy-based regimens for ES-SCLC often lead to myelosuppression, compromising medication compliance and prognosis. Trilaciclib is a CDK4/6 inhibitor, approved by NMPA in 2022 to decrease the incidence of chemotherapy-induced myelosuppression (CIM) in adult with ES-SCLC. This study aims to evaluate the efficacy and safety of preventive use of trilaciclib prior chemotherapy in Chinese ES-SCLC population under real-world settings. Methods: ES-SCLC patients suitable for combined treatment of trilaciclib and chemotherapy were enrolled in this study. Eligible participant received 240 mg/m2 of trilaciclib IV 4 h prior chemotherapy. The primary endpoint was the incidence rate of severe neutropenia (SN). The secondary endpoints included the occurrence of grade 3/4 hematologic adverse events (HAEs), administration rate of G-CSF and ESA, safety, and anti-tumor efficacy of chemotherapy. Results: A total of 201 ES-SCLC patients receiving at least one dose of trilaciclib combined with chemotherapy were included from 60 centers in China during March 10 2023 to August 10 2024, with median age of 65 (58, 71). Metastases occurred in 90.0% of the subjects at baseline, in which brain metastases accounted for 16%. 92.5% of the patients adopted platinum plus etoposide (E/P) regimen. The mean number of completed chemo-cycle was 3.0 (1.4). In Cycle 1, 1 case (0.6%) of SN occurred in patient receiving second-line (2L) treatment with E/P therapy. Grade 3/4 HAEs were reported in 5.4% of the patients in Cycle 1, including neutropenia (3.6%), anemia (1.2%) and thrombocytopenia (1.8%). During the whole treating period, a total of 5 cases (2.6%) of SN occurred, 4 of which received 2L treatment with E/P, while the remaining one received first-line cis-platinum therapy. 17.5% participants experienced grade 3/4 HAEs during the study, in which neutropenia, anemia and thrombocytopenia accounted for 8.2%, 9.3% and 3.1%, respectively. G-CSF and ESA were used in 2.6% and 1.0% of the patients. As for safety, grade ≥3 AEs were reported in 20.9% of the participants. No AEs-related treatment discontinuation happened. No serious AEs and death occurred. Among 48 patients included into tumor response analysis, the best response to chemotherapy was CR (8.3%), PR (43.8%), SD (39.6%) and PD (8.3%). The objective response rate (ORR) and disease control rate (DCR) reached 52.1% and 91.7%, respectively. Conclusions: Prophylactic administration of trilaciclib (240 mg/m2) prior chemotherapy exhibits superior myeloprotective effect and were well-tolerated in Chinese ES-SCLC population, providing evidence for clinical benefit of trilaciclib as a myelo-protectant. Citation Format: Ying Liu, Jianqiang Bi, Jianxin Chen, Meifang Chen, Xuesong Chen, Yongxing chen, Yinghua Ji, Yujie Jiang, Lu Li, Qin Liao, Sheng Lin, Jie Liu, Yi Liu, Yu Liu, Zhaoting Meng, Zhuqing Mu, Yunxiang Qi, Yanhong Shang, Ling Xu, Shufeng Xu, Lu Zheng, Jin Zhou, Ying Cheng. Preventive use of trilaciclib in Chinese patient with extensive-stage small cell lung cancer (ES-SCLC) receiving chemotherapy: A multi-center, single-arm, observational real-world study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7218.

Pathological complete response following addition of durvalumab to gemcitabine and cisplatin therapy for intrahepatic cholangiocarcinoma with Lynch syndrome-associated mismatch repair deficiency.

A 64-year-old man with a history of surgery for rectal cancer and colon cancer was referred for a hepatic mass identified on computed tomography (CT). He was diagnosed with unresectable intrahepatic cholangiocarcinoma (ICC) with perihilar and para-aortic lymph node metastases. After 4 cycles of gemcitabine and cisplatin combination therapy (GC therapy), follow-up CT showed slight enlargement of the primary tumor and a slight increase in carbohydrate antigen (CA) 19-9. Genetic testing was performed during GC therapy based on the strong family history of cancer. Germline pathogenic variant in MLH1 was identified, leading to the diagnosis of Lynch syndrome (LS) with mismatch repair deficiency (dMMR: loss of MLH1/PMS2). Durvalumab was added to GC therapy following regulatory approval in Japan. A significant reduction in tumor size and CA19-9 was observed after only two cycles of GC and durvalumab therapy. Continuous improvement was observed, and conversion surgery involving liver resection, partial inferior vena cava resection, and perihilar and para-aortic lymph nodes dissection was performed with curative intent. No malignant cells were found in any of the resected specimens, consistent with pathological complete response.

Effect of naringin and cisplatin combination on cell viability and cell death in bladder cancer cells

Bladder cancer is a prevalent malignancy characterized by high recurrence rates and limited therapeutic options, particularly due to resistance and toxicity associated with cisplatin therapy. Bladder cancer remains a significant global health concern, and while cisplatin is a cornerstone of treatment, its efficacy is often limited by resistance and toxicity. Therefore, there is a critical need for novel agents that can enhance cisplatin's effects while mitigating its drawbacks. This study investigates the potential of naringin, a natural flavonoid, to exhibit antiproliferative and proapoptotic effects in human bladder cancer cell lines (HTB-9 and HT-1376), both as a monotherapy and in combination with cisplatin. Cytotoxicity was assessed via the MTT ((3-(4,5-dimetiltiazol-2-il)-2,5 difeniltetrazoliumbromid) assay, and apoptosis was evaluated using Annexin V/PI staining and caspase 3/7 activation assays. Results demonstrated that naringin reduced cell viability in a dose-dependent manner in both cell lines. When combined with cisplatin, naringin significantly enhanced the antiproliferative and pro-apoptotic effects compared to either treatment alone. Caspase 3/7 activity was markedly elevated in the combination groups, indicating an amplified apoptotic response. These findings suggest that naringin can potentiate cisplatin’s efficacy and could serve as a promising adjunctive therapy in bladder cancer treatment. Further studies are warranted to explore the underlying mechanisms and potential clinical applications of naringin in enhancing cisplatin-based chemotherapy.

Real-world safety and efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy for locally advanced esophageal squamous cell carcinoma

BackgroundNeoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (DCF) has become the new standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). In a real-world setting, the efficacy, recurrence, and adverse events (AEs) remain unclear.MethodsThis retrospective cohort study included 86 patients who received neoadjuvant DCF followed by esophagectomy for resectable ESCC.ResultsFollowing neoadjuvant DCF treatment, 75 patients underwent R0 curative resection. At the median follow-up of 19.2 months, the median disease-free survival (DFS)/recurrence-free survival (RFS) was not yet reached, with estimated 3-year DFS/RFS rates of 65.2%, respectively. The incidence of primary tumor regression grading (TRG) grade 1a and pathological complete response (pCR) were 21.3% (16/75) and 14.7% (11/75), respectively. The estimated 1-year DFS/RFS rates were 93.8% for primary TRG grade 1a and 100% for pCR. Baseline elevated serum SCC-antigen levels were inversely associated with achieving primary TRG grade 1a or pCR. In 64 patients who did not achieve pCR, residual tumor cells in the lymph nodes (ypN; HR, 16.96; 95% CI, 2.11-136.12; P < 0.01) and Glasgow prognostic score (GPS; HR, 8.34; 95% CI, 1.73–40.31; P < 0.01) were independent predictors of shorter DFS/RFS. The most common grade ≥ 3 AEs were neutropenia (61.6%) and febrile neutropenia (26.7%), which were not associated with clinicopathological factors. The most common non-hematological AEs were appetite loss (9.3%), pulmonary embolism (8.1%), diarrhea (7.0%), and nausea (2.3%). Nine patients discontinued neoadjuvant DCF due to toxicities.ConclusionsNeoadjuvant DCF was effective and well-tolerated in real-world ESCC patients. Primary TRG grade 1a or pCR showed a favorable DFS/RFS, while positive ypN and GPS were independent risk factors for worse DFS/RFS.

VANGL2 downregulates HINT1 to inhibit the ATM-p53 pathway and promote cisplatin resistance in small cell lung cancer

Cisplatin is a first-line drug for the treatment of small cell lung cancer (SCLC). Although the majority of patients with SCLC initially respond to cisplatin therapy, cisplatin resistance readily develops, leading to tumor progression. Therefore, this study aims to elucidate the mechanisms underlying cisplatin resistance in SCLC. We found that VANGL2 is a poor prognostic factor and promotes cisplatin resistance in SCLC. Mechanistically, in cisplatin-resistant cells, VANGL2 overexpression leads to the autophagic degradation of HINT1. This reduction in HINT1 expression further reduces the phosphorylation of ATM and p53 induced by cisplatin-mediated DNA damage. The decreased phosphorylation of p53 inhibits downstream apoptotic pathways, thereby reducing cisplatin-induced apoptosis. In conclusion, VANGL2 regulates the ATM-p53 pathway-mediated apoptotic response of SCLC to cisplatin by downregulating HINT1, thereby promoting cisplatin resistance. Thus, VANGL2 may serve as a potential therapeutic target for reversing cisplatin resistance in SCLC patients.

Miltirone enhances the chemosensitivity of gastric cancer cells to cisplatin by suppressing the PI3K/AKT signaling pathway

BackgroundGastric cancer (GC) is one of the most common malignant tumors with poor survival. Although cisplatin is a first-line chemotherapy drug for GC, it still has the potential to develop drug resistance and side effects. Miltirone, extracted from Chinese herb Salvia miltiorrhiza Bunge, has been reported to significantly inhibit some types of cancer. However, its effects on GC have not been studied, the possible anti-tumor effects of miltirone in combination with cisplatin in GC patients have not been explored.Materials and methodsHuman GC cell lines AGS, HGC27, MKN45 and MGC803 cells were treated with miltirone and cisplatin individually or combinatorially. Cell proliferation assay, flow cytometric assay, colony formation assay and Western blot were employed to evaluate the cytotoxic effects under these treatments. Wound healing and transwell assays were used to examine the effects of miltirone and/or cisplatin on GC cell migration and invasion. RNA-seq analysis was used to determine miltirone’s potential target genes in AGS cells. GO analysis and molecular docking assay were used to determine the pathways affected by miltirone. Next, we examined changes in the selected pathway proteins. The in vivo animal model was verified the results of the in vitro experiments.ResultsMiltirone inhibited cell growth, migration, and invasion, as well as induced apoptosis in GC cells. In combinatorial treatments, miltirone synergistically enhanced cytotoxicity of cisplatin in GC cells. Moreover, the expression levels of 606 genes appeared to be significantly modulated by miltirone via RNA-seq analyses, and PI3K/AKT signaling pathway was found to refer to miltirone activity. Furthermore, miltirone together with cisplatin treatment significantly reduced the expression levels of p-PI3K, p-Akt, p-mTOR, while the total levels of PI3K and Akt remained unchanged. In addition, compared with the control group, the tumors growth was significantly suppressed in groups treated with the two agents alone or in combination, and even more so in the combination group in vivo.DiscussionMiltirone inhibited the proliferation of GC cells and significantly potentiates the anticancer activities of cisplatin by downregulating the PI3K/AKT signaling pathway. Combination therapy of miltirone and cisplatin represents a novel potential treatment of gastric cancer.

Oral Mucositis in Head and Neck Cancer Patients.

Oral Mucositis in Head and Neck Cancer Patients.

Modulation of Chemotherapy Sensitivity of Breast Cancer Cells through Transforming Growth Factor-beta Pathway-mediated Alterations in DNA Damage Response.

Chemotherapeutic drugs, like cisplatin, function by damaging genomic DNA, thus inducing cell apoptosis. Cancer cells can enhance their DNA repair capacity, leading to chemotherapeutic resistance. Nucleotide excision repair (NER) involves repairing DNA adducts and crosslinks caused by chemotherapeutic agents. Transforming growth factor-beta (TGF-β) pathway contributes to carcinogenesis, DNA repair alteration, and chemoresistance. However, the connection between TGF-β pathway, NER function alteration, and resistance to cisplatin therapy remains elusive. Therefore, the objective of current study was to fill this gap by assessing the impact of TGF-β inhibition and activation on cisplatin-induced antiproliferation, apoptosis, and DNA damage using the MTT assay, flow cytometry analysis, and COMET assay, respectively. Four NER genes, XPA, XPB, XPC, and XPF, were measured using Real-time Polymerase Chain Reaction (qPCR). MDA-MB-231 cell line was utilized as a model of breast cancer. Blockade of the TGF-β pathway strengthened cisplatin cytotoxicity, whereas induction of the TGF-β pathway suppressed cisplatin cytotoxicity. In cisplatin-treated breast cancer cells, DNA damage significantly increased upon the TGF-β pathway inhibition. Conversely, cisplatin-induced DNA damage decreased significantly upon TGF-β pathway stimulation. Finally, cisplatin caused an overexpression of the four NER genes which was curtailed and augmented by TGF-β inhibition and stimulation, respectively. Overall, this study presented evidence of the impact exerted by TGF-β pathway on NER and cisplatin sensitivity of breast cancer cells.

Locally advanced maxillary sinus cancer fed from the internal carotid artery.

Superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) is one of the effective treatments for advanced maxillary sinus cancer, and prospective trials have been conducted. However, treatment of cases with intraorbital infiltration or skull base infiltration that are fed from the internal carotid artery (ICA) may be problematic. In this study, we investigated the frequency, treatment, and prognosis of locally advanced maxillary sinus cancer fed from the ICA. This study included patients with locally advanced maxillary sinus cancer (clinical T4a or T4b) who underwent RADPLAT only via external carotid artery from January 2008 to January 2024. Nineteen of 44 cases were fed from the ICA (43.2%). Three-year overall survival (OS), three-year progression-free survival (PFS), and three-year local control rate (LCR) of all cases were 69.8%, 47.5%, and 61.8%, respectively. The three-year OS, PFS and LCR were equivalent between cases with or without feeding from the ICA. This study revealed the frequency and prognosis of locally advanced maxillary sinus cancer fed from the ICA. The prognosis was equivalent between cases with or without feeding from the ICA; therefore, it would be considered important to determine the tumor volume for each feeding blood vessel and assess the areas of dual perfusion.

Integrative analysis based on CRISPR screen identifies apilimod as a potential therapeutic agent for cisplatin-induced acute kidney injury treatment.

Acute kidney injury (AKI), a life-threatening side effect of cisplatin therapy, significantly limits the drug's therapeutic potential. In this study, we conducted a genome-wide CRISPR/Cas9 knockout screen in human renal tubular epithelial cells, integrating the results with transcriptome analyses and the Connectivity Map (CMap) database. Apilimod and elacridar emerged as the top two candidates of mitigating cisplatin-induced nephrotoxicity, with apilimod demonstrating superior efficacy in drug matrix experiments. Apilimod reduced cisplatin-induced apoptosis, inflammation and reactive oxygen species (ROS) generation. Transcriptome analyses suggested that apilimod may protect against cisplatin-induced nephrotoxicity via modulating lipid metabolism. In vitro experiments revealed that apilimod significantly ameliorated cisplatin-induced lipotoxicity by enhancing lipid clearance and upregulating PGC1α-mediated fatty acid oxidation. Mechanism experiments showed that apilimod induces the nuclear translocation of TFEB through the inhibition of its target, PIKfyve, thereby enhancing PGC1α expression and ameliorating lipotoxicity. These protective effects of apilimod were simulated by siRNA-mediated PIKfyve knockdown and diminished by the PGC1α inhibitor SR-18292 and siRNA targeting TFEB, confirming the role of the PIKfyve/TFEB/PGC1α signaling axis in apilimod's renoprotective effects. In vivo, apilimod alleviated apoptosis, inflammation, and lipid accumulation in a cisplatin-induced AKI mouse model. Additionally, apilimod treatment did not compromise the antitumor effect of cisplatin in cancer cells or tumor-bearing mice. Overall, our study suggests that apilimod could be a promising therapeutic agent for the treatment of cisplatin-induced AKI and revealed its underlying molecular mechanism.

Paving the way for better ototoxicity assessments in cisplatin therapy using more reliable animal models.

Cisplatin-induced hearing loss is a common and irreversible side effect affecting a significant proportion of cancer patients. While various strategies to mitigate this toxicity have been explored, there remains a critical need for effective treatments. A major challenge in developing new therapies is the lack of reliable animal models that accurately replicate the clinical use of cisplatin in humans, which typically involves multiple cycles of low-dose administration. Traditional models using high doses of cisplatin have resulted in high mortality and variable hearing loss, complicating the assessment of potential treatments. To address this, a multi-cycle model using lower cisplatin doses in mice was developed, providing hearing loss without mortality. However, variability in outcomes across different research groups persisted. In the present study, we optimize the multi-cycle model of cisplatin-induced ototoxicity by using clinical-grade cisplatin rather than laboratory-grade formulations. The use of clinical cisplatin ensures greater consistency, reliability, and relevance to human treatment protocols, as it adheres to the rigorous quality standards required for patient use. This new administration protocol will minimize variability across research laboratories and more accurately mimic the dosing regimens typically administered to cancer patients. Additionally, we have enhanced a zebrafish model for high-throughput screening of potential therapeutics, further improving the consistency of results. These improvements to the animal models are critical for accelerating the discovery and testing of therapies to prevent cisplatin-induced hearing loss, supporting the development of effective treatments for cancer patients undergoing cisplatin chemotherapy.

Strategies for early detection and detailed characterization of oral lesions and head and neck squamous cell carcinoma in Fanconi anemia patients.

Strategies for early detection and detailed characterization of oral lesions and head and neck squamous cell carcinoma in Fanconi anemia patients.