Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models.

The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment.

Genomic profiling of a multi-lineage and multi-passage patient-derived xenograft biobank reflects heterogeneity of ovarian cancer.

Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients.

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.

Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes.

A Promising New Model: Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers.

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established.

MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.

Background: Although the clinical application of PARP inhibitors has brought hope to ovarian cancer, the problem of its resistance has become increasingly prominent. Therefore, clinical experts have been focused on finding specific indicators and therapeutic targets that can be used for resistance monitoring of PARP inhibitors.

Results: By cfDNA detecting during Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer, we found the presence of MRE11:p.

BRD4 inhibition impairs DNA mismatch repair, induces mismatch repair mutation signatures and creates therapeutic vulnerability to immune checkpoint blockade in MMR-proficient tumors.

Background: Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect.

Codelivery of adavosertib and olaparib by tumor-targeting nanoparticles for augmented efficacy and reduced toxicity.

Ovarian cancer (OC) ranks first among gynecologic malignancies in terms of mortality. The benefits of poly (ADP-ribose) polymerase (PARP) inhibitors appear to be limited to OC with BRCA mutations. Concurrent administration of WEE1 inhibitors (eg, adavosertib (Ada)) and PARP inhibitors (eg, olaparib (Ola)) effectively suppress ovarian tumor growth regardless of BRCA mutation status, but is poorly tolerated.

Effect of previous Chlamydia Trachomatis infection on the outcomes of ivf/icsi treatment: a retrospective study.

Background: The impact of Chlamydia trachomatis infection (CT) on the outcomes of In-Vitro Fertilization / Intracytoplasmic sperm injection (IVF/ICSI) has been controversial.

Methods: A total of 431 infertility women aged 20-38 years with or without Chlamydia trachomatis infection before fresh/ frozen embryo transfer were included to investigate the effect of cured CT infection. The infected group was divided into two subgroups for ≤3 months and > 3 months according to the different intervals between Chlamydia trachomatis positive testing and embryo transfer.