Chemotherapy Research Articles

Efficacy of palifermin in the treatment of oral mucositis in non-hematopoietic stem cell transplant pediatric patients: experience of a single tertiary hospital

BackgroundSevere oral mucositis (OM) is one of the adverse events post-chemotherapy, radiation, and stem cell transplantation with major clinical and economic impact. The management of severe OM remains challenging. This study aimed to look for the benefit and clinical impact of palifermin for mucositis among the non-transplanted pediatric cancer population.MethodsThis is a descriptive retrospective study extended from 2016 to 2020 at Prince Sultan Military Medical City (PSMMC), in Saudi Arabia. During this period all pediatric patients (< 14 years of age) on chemotherapy and complicated by severe OM that required palifermin (35 courses), as off-labeled medication, were analyzed looking for the clinical demographics, primary diagnosis, chemotherapy agents used, effectiveness, and tolerability of palifermin.ResultsA total of 29 patients with severe OM received 35 palifermin courses. All of them received 60 mcg/kg/day IV for 3 consecutive days. 20% of them have acute lymphoblastic leukemia (ALL). We noticed that 60% of severe OM required palifermin post anthracycline while high-dose methotrexate aggravates the risk in 40% of them. Only 25.7% of the patients required TPN for a median duration of 5 days and 54.3% of them received opioids for a median duration of 4 days. Twenty patients (57.1%) had used antibiotics, 4 patients were on antifungal medication and 1 patient was on anti-viral medication concomitant with antibiotics.ConclusionPalifermin is safe and well tolerated and shows some effect in non-hematopoietic stem cell transplant pediatric patients with severe oral mucositis post-intensified chemotherapy or radiation therapy.

Efficacy Assessment of Sulfated Flavanol Functionalized Silver Nanoparticles against MCF-7 Breast Cancer

Aim: The present research work aims to formulate a cost-effective and less toxic drug for specific and selective delivery at the tumor site. Background: Existing therapeutics, such as chemo, surgery, etc., for fast-paced MCF-7 breast cancer, still face challenges, especially due to their toxic side effects. The unique properties of metal nanoparticles embedded in anti-oxidant plant polymers have sparked great interest in the formulation of less toxic-targeted drugs for cancer cure. Objective: The present work aims to synthesize a targeted formulation of colloidal nanosilver by surface engineering of silver nanoparticles using plant polymers in electrolytic deposition technique, developed indigenously at the institute lab. Methods: A current is passed through an elctrolyte, AgNO3, which splits it into ions. The positive ions of Ag deposit over LDPE wrapped carbon cathode and negative ion, NO3, is liberated. Ag+ ions get capped in-situ. These surface-modified silver nanoparticles formulate a colloidal solution. UV-visible and FTIR spectroscopy, TEM-EDX, and XRD were used to validate asprepared formulation and in vivo human tumor xenograft model in NOD-SCID mouse for efficacy against MCF-7 breast cancer. Results: The as-synthesized formulation consists of pure spherical poly-dispersed silver nanoparticles of average size 5.4 nm, coated with sulphated flavanols. The efficacy evaluation reported that it significantly, T/C = 0.53, reduced tumor volumes with a 100% survival rate and change in animal body weight &lt;4 gms. Conclusion: The as-synthesized formulation can be used as a potential neo-adjuvant or adjuvant drug along with existing therapeutics for MCF-7 breast cancer, significantly reducing the toxicity and cost.

Identifying memory genes in cancer drug tolerance

Identifying memory genes in cancer drug tolerance

Impact of Radiation Dose on the Survival of Patients With Non-small Cell Lung Cancer Treated With Palliative Intent: Results of a Multicenter Prospective Study.

Many patients with non-small cell lung cancer (NSCLC) receive palliative radiotherapy (RT). Several factors were analyzed to aid in prescribing an optimal treatment for these patients. This prospective observational multicenter study investigated several potential factors for associations with overall survival (OS) in 61 patients with NSCLC receiving palliative RT with or without chemotherapy (CT). Investigated factors included age, sex, performance status, history of smoking or alcohol, hemoglobin, co-morbidities, different clinical symptoms, and quality-of-life aspects. Median OS was 10.8 months, and OS rates at 6, 12, and 24 months were 58.5%, 42.5%, and 28.4%, respectively. On multivariate analysis, RT alone (without CT), RT doses ≤30 Gy, advanced tumor stage (stage IV), and poor emotional functioning at diagnosis were associated with significantly worse OS. Patients with NSCLC assigned to palliative RT may benefit from RT doses >30 Gy and additional CT. Sequential CT appears preferable, since concurrent CT increases esophageal toxicity.

Model based on ultrasound and clinicopathological characteristics for early prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer.

Accurate assessment of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is crucial for mitigating chemotherapy-related toxicity in patients who do not respond to the treatment. Conventional ultrasound (US) has become a pivotal method for evaluating treatment response due to its cost-effectiveness, convenience, and absence of ionizing radiation. The objective of this study was to develop a model combining US and clinicopathological characteristics at baseline, as well as US features after one cycle of NAC, to predict the pCR to NAC in BC. This retrospective study included 74 patients with invasive BC who underwent NAC from January 2022 to December 2023. Data from US and clinicopathological characteristics before NAC (pre-NAC) and US features after one cycle of NAC were collected from all patients. Univariate and multivariate analyses were used to screen the factors independently associated with pCR and to develop the prediction model. Receiver operating characteristic (ROC) curve analysis was performed, and the area under the curve (AUC), sensitivity, and specificity were calculated to assess the predictive efficiency. Four characteristics, including human epidermal growth factor receptor 2 (HER2)-positive [odds ratio (OR) 9.265; 95% confidence interval (CI): 1.617-53.095, P=0.012] and absence of posterior feature or posterior acoustic enhancement of the breast mass on the US pre-NAC (OR 9.435; 95% CI: 1.585-56.180, P=0.014), the maximum diameter reduction measured with the US (OR 1.081; 95% CI: 1.009-1.157, P=0.026), and the angular or spiculated margin of the breast lesion with the US after one cycle of NAC (OR 9.475; 95% CI: 1.247-71.969, P=0.030), were screened as independent predictors. The AUC, sensitivity, and specificity of the prediction model were 0.912, 90.0%, and 79.6%, respectively. US and clinicopathological characteristics at baseline and the US features after one cycle of NAC helped predict pCR for BC. The prediction model may enable early evaluation of the efficacy of treatment strategies and guide less invasive surgical options or personalized post-treatment plans.

Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial

BackgroundThe iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy. MethodsThis study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment. ResultsPatients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy. ConclusionsIP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment.(Japan Registry of Clinical Trials number, jRCTs031180141.)

Lipid-Based Niclosamide Delivery: Comparative Efficacy, Bioavailability, and Potential as a Cancer Drug

Niclosamide, an FDA-approved anti-parasitic drug, has demonstrated significant potential as a repurposed anti-cancer agent due to its ability to interfere with multiple oncogenic pathways. However, its clinical application has been hindered by poor solubility and bioavailability. Lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoemulsions (LNE), along with lipid prodrugs, have successfully been employed by researchers to overcome these limitations and improve niclosamide’s pharmacokinetic profile. Lipids are the core organic compounds which serve as the foundation of these advanced drug delivery methods and in turn play a critical role in enhancing niclosamide’s therapeutic efficacy through improving drug solubility and bioavailability. Lipid-based nanoparticles encapsulate niclosamide, protect it from degradation, facilitate drug delivery and release, and may facilitate targeted delivery in the future. While niclosamide holds significant potential as an anticancer agent due to its multi-pathway inhibitory effects, the challenges associated with its poor bioavailability and rapid clearance underscore the need for innovative delivery methods and chemical modifications to unlock its full therapeutic potential. This review aims to present the latest instances of lipid-based delivery of niclosamide and to compile successful strategies which may be employed when aiming to develop effective anticancer therapies.

Utilization of EGFR, ALK, and BRAF Inhibitors in the Treatment of Lung Cancer in Germany.

There is a lack of real-world data on the use of targeted cancer drugs requiring molecular tumor diagnostics in the treatment of lung cancer in Germany. We aimed to characterize the use of such drugs in lung cancer patients based on longitudinal analyses. Using the GePaRD database (claims data from ~20% of the German population) we identified lung cancer patients diagnosed in 2016 based on a previously developed algorithm and followed them until death, end of continuous insurance, or end of 2019. We determined the proportion of patients treated with at least one of the drugs under study (EGFR, ALK, and BRAF inhibitors). We described these patients regarding demographic characteristics, treatment patterns, and overall survival. We included 7833 incident lung cancer patients. Of these, 392 (5%) were treated with one of the drugs under study, the majority (62%) being female. In 314 out of the 392 patients (80%), the first dispensation was an EGFR inhibitor (afatinib: 54%, erlotinib: 33%), and in 72 patients (18%), it was an ALK inhibitor (crizotinib: 90%). The proportion of patients treated with these drugs was 4.8% in West Germany and 6.2% in East Germany. About half of these patients had chemotherapy before targeted therapy. Median overall survival after the first targeted therapy was 22 months. One twentieth of lung cancer patients diagnosed in 2016 in Germany received at least one EGFR, ALK, or BRAF inhibitor during follow-up. The proportion was higher in East than in West Germany. As the development and availability of new cancer drugs is a dynamic area, regularly updated utilization studies-ideally as cross-country-comparisons-are required.

Circulating microRNAs as a marker predicting chemoresistance to neoadjuvant chemotherapy in gastric cancer

Circulating microRNAs as a marker predicting chemoresistance to neoadjuvant chemotherapy in gastric cancer

Impact of anti-HER2 on response to neoadjuvant chemotherapy in HER2-positive breast cancer

Impact of anti-HER2 on response to neoadjuvant chemotherapy in HER2-positive breast cancer

Accuracy of MRI versus PET-CT in the prediction of treatment response to neo-adjuvant chemotherapy in breast cancer

Accuracy of MRI versus PET-CT in the prediction of treatment response to neo-adjuvant chemotherapy in breast cancer

Current status of postoperative morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer with peritoneal metastasis

Current status of postoperative morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer with peritoneal metastasis

Prevalence of HER3 Expression in Pancreatic Cancer Patients Treated With Systemic Chemotherapy.

Although activation of human epidermal growth factor receptor 3 (HER3) is linked to resistance to targeted therapies in several cancer types, the HER3 expression profile during pancreatic cancer treatment remains unknown. We evaluated the HER3 expression status after chemotherapy for pancreatic cancer and its association with clinicopathological features and clinical outcomes. We included patients with pancreatic cancer who underwent chemotherapy and whose post-treatment archival tissue specimens were collected. HER3 expression was retrospectively assessed by immunohistochemistry scoring (0, 1+, 2+, and 3+) of the membranous staining intensity. HER3 expression after chemotherapy was evaluated in 41 patients, with matched-pair analysis in five patients before and after chemotherapy. HER3 expression was observed in most of the patients after chemotherapy, demonstrating IHC scores of ≥ 1+ and ≥ 2+ in 40 (98%) and 26 (63%) of 41 patients, respectively. Of the 38 patients with adenocarcinoma, the median overall survival in the HER3 (2+/3+) and HER3 (0/1+) groups was 21.0 and 17.1 months, respectively. The comparison of HER3 expression before and after chemotherapy performed in five cases revealed that scores changed from 2+/3+ to 0/1+ in one case, 0/1+ to 2+/3+ in another case, and remained at 2+/3+ in three cases. Cancer genome profiling tests in eight cases found no HER3 amplification or mutation, and seven of these cases had adenocarcinomas with KRAS and TP53 mutations. A high prevalence of HER3 expression was observed in pancreatic cancer patients after chemotherapy. Our findings indicate that HER3 is a potential therapeutic target for pancreatic cancer, deserving further clinical investigation.

Factors influencing response to neoadjuvant chemotherapy in breast cancer and its impact on long-term survival: A perspective from an Indian cohort

Factors influencing response to neoadjuvant chemotherapy in breast cancer and its impact on long-term survival: A perspective from an Indian cohort

Oncological safety of response-guided breast conserving surgery compared to mastectomy after neoadjuvant chemotherapy in breast cancer: a nationwide population-based target trial emulation

Oncological safety of response-guided breast conserving surgery compared to mastectomy after neoadjuvant chemotherapy in breast cancer: a nationwide population-based target trial emulation

Efficacy and Safety Evaluation of Immune Checkpoint Inhibitors in Combination With Chemotherapy for Extensive Small Cell Lung Cancer: Real-World Evidence.

Extensive small cell lung cancer (ES-SCLC) are currently managed using first-line chemotherapy options, including atezolizumab (Atezo) plus etoposide and carboplatin (CE) or durvalumab (Durva) plus etoposide with either cisplatin (PE) or carboplatin (CE). However, a definitive distinction in therapeutic effects between Atezo and Durva in these regimens remains unestablished. We analyzed data from 100 patients diagnosed with ES-SCLC who received immune checkpoint inhibitors (ICIs) as first-line chemotherapy. Among them, 70 were administered Atezo + CE, 12 received Durva + PE, and 18 received Durva + CE. We assessed the efficacy of the two ICIs across various factors. The progression-free survival (PFS) and overall survival (OS) did not significantly differ between Atezo + CE and Durva + CE/PE as first-line chemotherapy treatments for SCLC. We observed no significant differences in age, sex, performance status (PS), liver metastasis, bone metastasis, or platinum-based agent usage between the treatment cohorts. However, a marked improvement in PFS and OS was observed in the solitary patient with brain metastasis treated with Atezo + CE. The primary distinction between these treatments was observed in the management of patients with brain metastasis. The literature lacks comparative studies on the effects of first-line ICI treatment on the central nervous system, rendering our findings significant in clinical practice. Despite the retrospective nature of this study and the potential for various biases, we recommend the preferential use of Atezo + CE in patients with brain metastasis to potentially enhance prognosis.

The role of baseline peripheral neutrophil to lymphocyte ratio in predicting response to neoadjuvant chemotherapy in breast cancer

The role of baseline peripheral neutrophil to lymphocyte ratio in predicting response to neoadjuvant chemotherapy in breast cancer

Long non-coding RNA AC105118.1 affects glycolysis to facilitate oxaliplatin resistance in colorectal cancer cells by modulating the miR-378a-3p/KIF26B axis

BackgroundOxaliplatin is a first-line chemotherapy drug for colorectal cancer (CRC), but many patients eventually lose treatment efficacy due to acquired resistance. AC105118.1 is a long non-coding RNA with unknown biological function. This research attempts to probe into the molecular regulatory mechanism of AC105118.1 in CRC oxaliplatin resistance. MethodsThe expression level of AC105118.1 in CRC tissues and cells was measured based on The Cancer Genome Atlas (TCGA) data and quantitative reverse transcription polymerase chain reaction (qRT-PCR). We utilized dual-luciferase assay and RNA immunoprecipitation to analyze the interaction between AC105118.1, miR-378a-3p, and their downstream target KIF26B. CCK-8, colony formation assay, and flow cytometry were employed to assess the half inhibitory concentration (IC50), cell proliferation, and apoptosis rate of HCT116/L-OHP cells treated with oxaliplatin. The glycolysis evaluation was completed by measuring the extracellular acidification rate (ECAR), glucose consumption, lactate production, and glycolysis-related proteins (HK2, GLUT1, and LDHA). TUNEL staining was used to detect the level of apoptosis. ResultsAC105118.1 was specifically upregulated in CRC tissues and cells. AC105118.1 indirectly facilitated the expression of miRNA target gene KIF26B by sequestering miR-378a-3p. In HCT116/L-OHP cells, transfection with si-AC105118.1 resulted in a decrease in glycolysis level, a lower maximum IC50 required for oxaliplatin-treated cells, inhibited cell proliferation, and an increase in apoptosis rate. All of these effects were alleviated when simultaneously transfecting miR-378a-3p inhibitor or oe-KIF26B. Knockdown of AC105118.1 significantly inhibited oxaliplatin resistance to CRC in mice. ConclusionAC105118.1 facilitates glycolysis and increases CRC cells’ resistance to oxaliplatin by targeting the miR-378a-3p/KIF26B axis. The present work shed new insights into the function and mechanism of AC105118.1 in molecular function and suggested that the AC105118.1/miR-378a-3p/KIF26B axis is a promising target for intervening CRC oxaliplatin resistance.

Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Intracellular mechanistic insights into cRGD-modified Bi2Se3 nanofoams for enhanced photothermal therapy via exocytosis inhibition.

The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of Bi2Se3 nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking. Our findings reveal that the cRGD-coated Bi2Se3 nanofoams are internalized through three distinct endocytosis pathways: Rab34-mediated macropinocytosis, caveolae-dependent, and clathrin-dependent endocytosis. These nanofoams then accumulate in lysosomes via autophagy. Furthermore, inhibiting exocytosis reduces the loss of these nanofoams from cancer cells, enhancing photothermal and chemotherapy effects. This exocytosis-inhibiting strategy demonstrates significant potential for cancer therapy, validated by successful in vitro and in vivo results.