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Journal of Nanobiotechnology Jun 2024Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic...
BACKGROUND
Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement.
RESULTS
This unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (< 5% O). These features correlate with the drug responses and clinical diagnosis from each patient's histopathological report.
CONCLUSIONS
Overall, we demonstrate the influence of tumor differentiation status on treatment responses, which has been rarely carried out in the previous reports. To the best of our knowledge, this is the first report demonstrating extensive work on development of microfluidic based oral cancer spheroid model for personalized combinatorial drug screening. Furthermore, the obtained clinical correlation of drug screening data represents a significant advancement over previously reported personalized spheroid-based microfluidic devices. Finally, the maintenance of patient-derived spheroids with high viability under oral cancer relevant oxygen levels of less than 5% O is a more realistic representation of solid tumor microenvironment in our developed device.
Topics: Humans; Mouth Neoplasms; Spheroids, Cellular; Lab-On-A-Chip Devices; Neoplastic Stem Cells; Drug Screening Assays, Antitumor; Antineoplastic Agents; Precision Medicine; Printing, Three-Dimensional; Fluorouracil; Paclitaxel
PubMed: 38890730
DOI: 10.1186/s12951-024-02625-y -
Cancer Medicine Jun 2024Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma...
Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.
INTRODUCTION
Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen.
METHODS
Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors.
RESULTS
Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm.
CONCLUSION
PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.
Topics: Humans; Male; Penile Neoplasms; Middle Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Paclitaxel; Cisplatin; Serpins; Aged; Neoplasm Staging; Biomarkers, Tumor; Prognosis; Retrospective Studies; Adult
PubMed: 38888362
DOI: 10.1002/cam4.7353 -
Kardiologia Polska Jun 2024
Long-term outcomes following paclitaxel-coated balloons versus thin-strut drug eluting stents for treatment of in-stent restenosis in Chronic Coronary Syndrome (CCS Dragon-Registry).
PubMed: 38887780
DOI: 10.33963/v.phj.101064 -
BMC Pulmonary Medicine Jun 2024Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential...
BACKGROUND
Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin.
CASE PRESENTATION
The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital's cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents.
CONCLUSION
Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment.
Topics: Humans; Lung Diseases, Interstitial; Drug-Eluting Stents; Sirolimus; Eosinophilia; Male; Tomography, X-Ray Computed; Percutaneous Coronary Intervention; Aged
PubMed: 38886703
DOI: 10.1186/s12890-024-03101-x -
Scientific Reports Jun 2024In vitro evolution and whole genome analysis has proven to be a powerful method for studying the mechanism of action of small molecules in many haploid microbes but has...
In vitro evolution and whole genome analysis has proven to be a powerful method for studying the mechanism of action of small molecules in many haploid microbes but has generally not been applied to human cell lines in part because their diploid state complicates the identification of variants that confer drug resistance. To determine if haploid human cells could be used in MOA studies, we evolved resistance to five different anticancer drugs (doxorubicin, gemcitabine, etoposide, topotecan, and paclitaxel) using a near-haploid cell line (HAP1) and then analyzed the genomes of the drug resistant clones, developing a bioinformatic pipeline that involved filtering for high frequency alleles predicted to change protein sequence, or alleles which appeared in the same gene for multiple independent selections with the same compound. Applying the filter to sequences from 28 drug resistant clones identified a set of 21 genes which was strongly enriched for known resistance genes or known drug targets (TOP1, TOP2A, DCK, WDR33, SLCO3A1). In addition, some lines carried structural variants that encompassed additional known resistance genes (ABCB1, WWOX and RRM1). Gene expression knockdown and knockout experiments of 10 validation targets showed a high degree of specificity and accuracy in our calls and demonstrates that the same drug resistance mechanisms found in diverse clinical samples can be evolved, discovered and studied in an isogenic background.
Topics: Humans; Haploidy; Drug Resistance, Neoplasm; Antineoplastic Agents; Genome, Human; Whole Genome Sequencing; Cell Line
PubMed: 38886371
DOI: 10.1038/s41598-024-63943-7 -
Frontiers in Oncology 2024Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands....
Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands. However, these tumors can potentially emerge in any location with minor salivary glands, including the nasopharynx. This report presents two cases of HCCC in females aged 61 and 72 years, with both tumors approximately 4 cm in size. In the first case, a 72-year-old female presented with recurrent bilateral epistaxis. Imaging studies revealed a nasopharyngeal mass, surgically excised, and histopathological analysis confirmed HCCC. Postoperatively, the patient received combined chemotherapy and radiotherapy, achieving a recurrence-free status 2.5 years later. The second case involves a 61-year-old female with a two-year history of bloody nasal discharge. Imaging studies identified a nasopharyngeal lesion, surgically removed, and histopathological examination confirmed HCCC. This patient underwent radiotherapy followed by combination chemotherapy with paclitaxel and carboplatin, displaying no signs of recurrence upon reevaluation after 10 months. These cases highlight the successful management of HCCC through a comprehensive, multimodal approach, integrating surgical intervention and adjuvant therapy. The favorable outcomes emphasize the significance of a thorough treatment strategy for HCCC in the nasopharynx, providing valuable insights for clinicians. Further studies are essential to enhance our understanding of this rare entity and refine treatment protocols for optimized patient outcomes.
PubMed: 38884096
DOI: 10.3389/fonc.2024.1384913 -
Geburtshilfe Und Frauenheilkunde Jun 2024The presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical...
Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Neoadjuvant Chemotherapy Prior to Definitive Radiochemotherapy in Patients with Locally Advanced Cervical Cancer.
The presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical Oncology (ESMO) is likely to change the therapy for locally advanced cervical cancer. In the GCIG INTERLACE trial, six cycles of neoadjuvant chemotherapy administered weekly and consisting of carboplatin AUC2 and paclitaxel 80 mg/m followed by definitive radiochemotherapy with pelvic radiotherapy (40 - 50.4 Gray) and cisplatin (40 mg/m once a week for 5 weeks) and brachytherapy (total dose EQD2 at least 78 Gy at point A) (experimental arm) were compared with definitive radiochemotherapy alone (standard arm) in patients with locally advanced cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] 2008 stage IB1/node positive, IB2, II, IIIB and IVA) and was found to be significantly superior with significantly longer recurrence-free survival (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.64 - 0.91; p = 0.013) and significantly longer overall survival rates (HR 0.61; 95% CI: 0.40 - 0.91; p = 0.04) after 5 years' follow-up. After considering the results of the GCIG INTERLACE trial published at the congress, the Uterus Commission of the AGO is of the opinion that neoadjuvant chemotherapy with carboplatin AUC2 and paclitaxel 80 mg/m d1, q7, x6 may be offered to patients with locally advanced cervical cancer (FIGO stage IB1/node positive, IB2, II, IIIB and IVA) in addition to the current standard therapy after the patient has been informed about the risks, with the decision taken on a case-by-case basis. However, before this approach can be discussed at guideline level or defined as the new therapy standard, it will be necessary to wait until the data from the full publication are available.
PubMed: 38884027
DOI: 10.1055/a-2279-3163 -
Cureus May 2024Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced...
Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced vulvar cancer. Here, we report the case of a 55-year-old woman diagnosed with advanced vulvar cancer with inguinal and pelvic lymph node metastasis. She exhibited cancerous labia, which were entirely covered with ulcerated and exophytic lesions of squamous cell carcinoma, and underwent systemic chemotherapy consisting of combined paclitaxel-cisplatin. After eight cycles of this regimen, the tumors had nearly regressed, and we performed a wide local vulvectomy with a plastic musculocutaneous flap. Pathological examination revealed no residual carcinoma in the excised labia, indicating that the chemotherapy elicited a pathological complete response. The paclitaxel-cisplatin regimen may provide sufficient efficacy for selected patients with stage IVB vulvar cancer. In addition, surgical strategies should be tailored to avoid complications associated with extensive surgery and more emphasis should be placed on the patient's expected quality of life.
PubMed: 38882968
DOI: 10.7759/cureus.60432 -
Therapeutic Advances in Medical Oncology 2024In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the...
French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients.
CONTEXT
In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions.
OBJECTIVES
GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients.
DESIGN
All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened.
METHODS
This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals.
RESULTS
The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38-0.77, = 0.001), with a median OS of 6.2 months ( 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration.
CONCLUSION
The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.
PubMed: 38882442
DOI: 10.1177/17588359241259635 -
Translational Cancer Research May 2024Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase...
BACKGROUND
Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents.
METHODS
CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle.
RESULTS
The IC value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX).
CONCLUSIONS
The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.
PubMed: 38881946
DOI: 10.21037/tcr-23-2169