flura-seq for evaluating the effects of different hyperthermic intraperitoneal chemotherapy regimens on the transcriptome of pseudomyxoma peritonei

Conditions: Pseudomyxoma Peritonei

Summary: the main objective of this study is to combine hipec regimens with flura-seq to detect the effects of different hipec regimens (cisplatin vs. cisplatin+ docetaxel) on the nascent transcriptome of pmp tumors, so as to quantitatively assess the efficacy of different hipec regimens in the early stage, and to lay the foundation for optimizing the hipec regimens and exploring new therapeutic targets.

1. participants: ① diagnosed pmp patients; ② patients can receive crs+hipec treatment. 2. trial protocol: the patients will be randomly divided into cisplatin group and cisplatin + docetaxel group. preoperative intravenous bolus injection of 5-fu (400 mg/m2) will be given before crs+hipec treatment. after crs, the patients will be treated with cisplatin or cisplatin + docetaxel hipec, respectively. cisplatin 120 mg or docetaxel 120 mg + cisplatin 120 mg will be added to 3,000 ml of saline, heated to 43 ℃, and perfused at a flow rate of 400 ml/min for 60 min. 3. sample collection: tumor tissue samples (5-10 g) will be collected before and after hipec treatment, and will be stored at 80 ℃ for nascent transcriptome sequencing. 4. sequencing analysis of nascent transcriptome: using high-throughput sequencing technology, the rna extracted from tumor tissue samples before and after treatment with cisplatin or cisplatin + docetaxel hipec will be sequenced by flura-seq to analyze the changes of newly synthesized transcripts in tumor tissue during hipec. 5. data analysis: the sequencing data will be processed and analyzed by bioinformatics methods. the differentially expressed genes in cisplatin group and cisplatin + docetaxel group will be compared to evaluate the efficacy of different hipec regimens on pmp. functional annotation and pathway analysis of differentially expressed genes will be performed to explore molecular therapeutic targets for pmp-specific rna. 6. treatment regimen for poor therapeutic effect: the study will not change the patient's existing hipec regimen. if the results show that hipec is not effective in treating the patient, it means that the drug is not effective for the patient during subsequent chemotherapy, and the chemotherapy regimen can be adjusted accordingly based on the flura-seq results.

Eligibility criteria:
inclusion criteria: * age 18-75 years old, regardless of gender and race; * pathologically confirmed as pseudomyxoma peritonei; acceptable for crs+hipec treatment; * kps score ≥ 60, with expected survival time more than 12 months; * the functions of important organs are basically normal, with no significant abnormalities in liver or kidney function; * no history of allergy to biological products; * no serious bacterial or viral infection; * non-pregnancy and lactation; * the patient or his/her delegate understands and cooperates with the treatment and signs the informed consent for the treatment. exclusion criteria: * highly allergic or with a history of severe allergies, especially to biological products; * shock, systemic failure, unstable vital signs, and inability to cooperate with the examination; * those who have mental or psychological diseases and cannot cooperate with treatment and curative effect evaluation; * t-lymphocyte carcinoma/tumor; * patients with systemic infection or severe local infection requiring anti-infection treatment; * complicated with dysfunction of heart, lung, brain, kidney, liver and other important organs; * coagulation disorders (e.g., hemophilia); * infectious diseases (e.g. hiv, rpr, active tb, etc.); * pregnant or lactating women, or women who have pregnancy plans within half a year; * patients who are taking immunosuppressive drugs or long-term anti-rejection drugs after organ transplantation; * patients with severe autoimmune diseases; * any life-threatening disease, physical condition or organ system dysfunction that the researcher believes may damage the safety of subjects and expose the research results to unnecessary risks; drug-dependent persons; * patients and/or authorized family members who refuse or do not actively sign the informed consent; * participants in other clinical studies within 3 months.

Keywords: flura-seq pmp hipec fluorouracil-labeled nascent rna technology