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Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

ABSTRACT: Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

PROVIDER: PRJNA991486 | ENA |

REPOSITORIES: ENA

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Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

Project description:Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal (IP) delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by IP administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly IP paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous (IV) to IP administration, IP delivery of paclitaxel was more effective with reduced systemic side effects in mice. Given the established safety record of IP paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of IP paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of IP paclitaxel in a prospective clinical trial.

2023-07-07 | GSE236502 | GEO

Phase I trial of intraperitoneal paclitaxel combinated with mFOLFOX6 or CapeOX for colorectal cancer with peritoneal metastasis

Project description:Interventions: 20mg/m2 of weekly Intraperitoneal paclitaxel Primary outcome(s): Safety Study Design: Single arm Non-randomized

| 2638181 | ecrin-mdr-crc

RNA-Seq Analysis of Paclitaxel-Resistant PDX Models in Mice

Project description:In this study, we aimed to investigate the gene expression changes associated with the development of paclitaxel resistance in patient-derived xenograft (PDX) models. We established paclitaxel-resistant PDX models in mice by administering 10 mg/kg of paclitaxel via intraperitoneal injection once a week. The treatment continued until the sixth generation of the PDX models was successfully established. RNA sequencing was performed on samples from the first generation (control and treated groups) and the sixth generation (control and treated groups) to identify differentially expressed genes and pathways involved in drug resistance. Our findings provide insights into the molecular mechanisms underlying paclitaxel resistance and may inform the development of more effective therapeutic strategies.

2024-08-10 | GSE272834 | GEO

Mucinous colorectal adenocarcinoma

Project description:Mucinous colorectal adenocarcinoma

| PRJNA992109 | ENA

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel In Patients With Peritoneal Carcinomatosis

Project description:Peritoneal carcinomatosis (PC) is a miserable disease with poor treatment outcome. Intraperitoneal administration of anticancer drugs enables an extremely high concentration of drugs to directly contact the target cancer lesions in the peritoneal cavity. However, its effectiveness is limited by the intraperitoneal distribution and penetration of the drug. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative intraperitoneal chemotherapy concept that enhances efficacy by taking advantage of the physical properties of gas and pressure. Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC) may further enhance these benefits. This research study serves to determine the safety profile and tolerability of PIPAC/ePIPAC with paclitaxel. It will determine the maximal tolerated dose (MTD) and evaluate the safety and tolerability, and pharmacokinetics of PIPAC/ePIPAC paclitaxel in pre-treated patients with peritoneal carcinomatosis (PC). It may offer a novel and effective option of treatment for patients with PC, who, at present have limited options involving the use of systemic chemotherapy and who suffer from poor life expectancy and poor quality of life.

| 2732287 | ecrin-mdr-crc

Paclitaxel resistance in ovarian cancer increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control

Project description:The microtubule-stabilising drug paclitaxel has activity in relapsed ovarian cancer. However, resistance frequently develops. Oncolytic adenoviruses are a novel cancer therapy, and replicate selectively within and lyse malignant cells, leading to productive infection of neighbouring cells. We found increased efficacy of adenoviruses of multiple subtypes in paclitaxel-resistant ovarian cancer cells. There was increased expression of a key adenovirus receptor, CAR (coxsackie adenovirus receptor), due to increased transcription that resulted from histone modification. Moreover, CAR transcription increased in intraperitoneal xenografts with acquired paclitaxel resistance and in tumours from patients with paclitaxel-resistant ovarian cancer. Finally, we identified dysregulated cell cycle control as a second mechanism of increased adenovirus efficacy in paclitaxel-resistant ovarian cancer and that inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases oncolytic adenovirus efficacy via at least two separate mechanisms. Parental SKOV3 and paclitaxel-resistant SKOV3-TR cells were analysed in duplicate

2015-12-10 | E-GEOD-54772 | biostudies-arrayexpress

Clinical comparative study of neoadjuvant intraperitoneal chemotherapy based on paclitaxel for peritoneal metastasis of colorectal cancer

Project description:Interventions: Control group:Empirical systemic standard regimen neoadjuvant chemotherapy (FolFox);Experimental group:Paclitaxel intraperitoneal chemotherapy combined with systemic standard regimen for neoadjuvant chemotherapy Primary outcome(s): Overall Response Rate;progression-free survival, PFS Study Design: Parallel

| 2696780 | ecrin-mdr-crc

Paclitaxel resistance in ovarian cancer increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control

2015-12-10 | GSE54772 | GEO

Proteome profiling of mucinous and non-mucinous colorectal cancer

Project description:Mucus is associated with poor prognosis of colorectal cancer, but its mechanism remains unclear. The aim of this study was to reveal the key proteins in mucinous colorectal cancer. In this study, high-resolution liquid chromatography tandem mass spectrometry (LC-MS / MS) combined with quantitative 6-plex tandem mass mass tag labeling was used to profile protein changes in the left and right sides of mucinous and non-mucinous colorectal cancer tissues. A total of 7432 proteins were identified and analyzed.

2020-11-28 | PXD022802 |

Expression data of mouse mucinous lung tumors

Project description:Transgenic mice (Scgb1a1-rtTA/[tetO]-KRAS.G12D/Nkx2-1+/-) develop mucinous lung tumors. Gene expression analysis was performed using mRNAs from the whole lungs of the mice compared to that of the control mice. We used microarrays to detail the global program of gene expression underlying development of mucinous lung tumors and identified distinct classes of up-regulated genes during this process. mRNAs were isolated from the whole lungs of the transgenic mice (Scgb1a1-rtTA/[tetO]-KRAS.G12D/Nkx2-1+/-) after 2 months doxycycline administration and hybridized on Affymetrix microarrays. We sought to identify genes induced in mucinous lung tumors.

2012-08-31 | E-GEOD-40508 | biostudies-arrayexpress

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