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The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women, by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.

The expression of drug resistance genes including
π
and
were detected with immunohistochemistry in a tissue microarray. Drug sensitivity tests included those for paclitaxel, epirubicin, carboplatin, vinorelbine, and fluorouracil and were conducted on primary cancer tissue cells and cell lines, including the T47D, BT-474, and MDA-MB-231 cells and human breast cancer xenografts in nude mice.

The different drug resistant genes
π
and
were differentially expressed among different molecular subtypes of breast cancers (
< 0.05). Positive expression of CD133 was highest in basal-like breast cancer (
< 0.05). Kaplan-Meier survival analysis showed that positive expressions of Topo II and CD133 both correlated with shorter disease-free survival (DFS) (
< 0.05) and overall survival (
< 0.05), and positive expression of LRP correlated only with shorter DFS (
< 0.05). BT-474 showed chemosensitivity to paclitaxel and epirubicin, while MDA-MB-231 showed chemosensitivities to paclitaxel, epirubicin, carboplatin, and fluorouracil (T/C ≤ 50%). The basal-like and HER2+ breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells (
< 0.05).

The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.
The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.
Currently, there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors (ICIs) for patients with gastric cancer (GC). Homologous recombination deficiency (HRD) can modify the tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes and therefore might serve as a biomarker of immunotherapeutic response. We aimed to analyze the mutational pattern of HR-associated genes in Chinese patients with GC and its relevance to the tumor immune profile and clinical immunotherapeutic response.

A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort comprising 484 Chinese patients with GC. Correlations between HR gene mutations and tumor immunity or clinical outcomes were identified
bioinformatic analysis using 2 GC genomic datasets (TCGA and MSK-IMPACT).

Fifty-one of the 484 (10.54%) patients carried at least one somatic mutation in an HR gene;
(16/484, 3.31%) was among the most frequently mutated HR genes in the Chinese cohort. Mutations in HR genes were associated with elevated tumor mutational burden, enhanced immune activity, and microsatellite instability status. In the MSK-IMPACT cohort comprising 49 patients with stomach adenocarcinoma or gastroesophageal junction adenocarcinoma treated with ICIs, patients with HR-mut GC (
= 12) had significantly better overall survival than those with HR-wt GC (
= 37) (log-rank test,
< 0.05).

Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy.
Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy.
Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma, owing to the presence of the blood-brain barrier and the activity of P-gp, which pumps its substrate back into the systemic circulation. The aim of the present study was to develop an intravenous formulation of HM30181A (HM) to inhibit P-gp in the brain to effectively deliver paclitaxel (PTX) for the treatment of malignant glioma.

Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies i) spray-drying [polyvinlypyrrolidone (PVP)-HM] and ii) solvent evaporation [HP-β-cyclodextrin (cyclodextrin)-HM]. The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer cells. Blood and brain pharmacokinetic parameters were also determined, and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse model.

Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity
, cyclodextrin-HM had a higher maximum tolerated dose in mice than did PVP-HM. Pharmacokinetic study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg, and the mice began to lose weight at doses above this level. Cyclodextrin-HM (10 mg/kg) administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model, according to both tumor volume measurement and survival time (
< 0.05).

In a mouse orthotopic brain tumor model, the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.
In a mouse orthotopic brain tumor model, the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.
Chromosomal instability (CIN) is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes, frequently observed in cancer cell populations and is associated with poor prognosis, metastasis, and therapeutic resistance. Breast cancer (BC) is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens. However, paradoxical associations between extreme CIN and improved outcome have been observed.

This study aimed to 1) evaluate CIN levels and clonal heterogeneity (CH) in MCF7, ZR-751, MDA-MB468, BT474, and KPL4 BC cells treated with low doses of tamoxifen (TAM), docetaxel (DOC), doxorubicin (DOX), Herceptin (HT), and combined treatments (TAM/DOC, TAM/DOX, TAM/HT, HT/DOC, and HT/DOX) by using fluorescence
hybridization (FISH), and 2) examine the association with response to treatments by comparing FISH results with cell proliferation.

Intermediate CIN was linked to drug sensitivity according to three characteristics estrogen receptor α (ERα) and HER2 status, pre-existing CIN level in cancer cells, and the CIN induced by the treatments. ERα+/HER2
cells with intermediate CIN were sensitive to treatment with taxanes (DOC) and anthracyclines (DOX), while ERα
/HER2
, ERα+/HER2+, and ERα-/HER2+ cells with intermediate CIN were resistant to these treatments.

A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.
A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.
Pancreatic ductal adenocarcinoma (PDAC) is a disease with high mortality. Many so-called "junk" noncoding RNAs need to be discovered in PDAC. The purpose of this study was therefore to investigate the function and regulatory mechanism of the long noncoding RNA MEG3 in PDAC.

The Gene Expression Omnibus database (GEO database) was used to determine the differential expression of long noncoding RNAs in PDAC, and MEG3 was selected for subsequent verification. Tissue and cell samples were used to verify MEG3 expression, followed by functional detection
and
. Microarrays were used to characterize long noncoding RNA and mRNA expression profiles. Competing endogenous RNA analyses were used to detect differential MEG3 and relational miRNA expression in PDAC. Finally, promoter analyses were conducted to explain the downregulation of MEG3 PDAC.

We generated a catalogue of PDAC-associated long noncoding RNAs in the GEO database. The ectopic expression of MEG3 inhibited PDAC growth and metastasis
and
, which was statistically significant (
< 0.05). Microarray analysis showed that multiple microRNAs interacted with MEG3. We also showed that MEG3, as a competing endogenous RNA, directly sponged miR-374a-5p to regulate PTEN expression. Plumbagin Apoptosis related chemical The transcription factor, Sp1, recruited EZH2 and HDAC3 to the promoter and transcriptionally repressed MEG3 expression. Finally, clinical data showed that MEG3 and miR-374a-5p expressions were correlated with clinicopathological features. Statistically, Sp1, EZH2, HDAC3, and miR-374a-5p were negatively correlated with MEG3 (
< 0.05).

Reduced MEG3 levels played a crucial role in the PDAC malignant phenotype, which provided insight into novel and effective molecular targets of MEG3 for pancreatic cancer treatment.
Reduced MEG3 levels played a crucial role in the PDAC malignant phenotype, which provided insight into novel and effective molecular targets of MEG3 for pancreatic cancer treatment.
Epigenetic aberration plays an important role in the development and progression of hepatocellular carcinoma (HCC). However, the alteration of RNA N6-methyladenosine (m6A) modifications and its role in HCC progression remain unclear. We therefore aimed to provide evidence using bioinformatics analysis.

We comprehensively analyzed the m6A regulator modification patterns of 605 HCC samples and correlated them with metabolic alteration characteristics. We elucidated 390 gene-based m6A-related signatures and defined an m6Ascore to quantify m6A modifications. We then assessed their values for predicting prognoses and therapeutic responses in HCC patients.

We identified 3 distinct m6A modification patterns in HCC, and each pattern had distinct metabolic characteristics. The evaluation of m6A modification patterns using m6Ascores could predict the prognoses, tumor stages, and responses to sorafenib treatments of HCC patients. A nomogram based on m6Ascores showed high accuracy in predicting the overall survivalderstanding of m6A modifications in HCC, and helps predict the prognosis and treatment response.
HCCs harbored distinct m6A regulator modification patterns that contributed to the metabolic heterogeneity and diversity of HCC. Development of m6A gene signatures and the m6Ascore provides a more comprehensive understanding of m6A modifications in HCC, and helps predict the prognosis and treatment response.Exhausted T cells are a group of dysfunctional T cells, which are present in chronic infections or tumors. The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity, reduced cytokine production, and upregulation of multiple inhibitory molecular receptors (e.g., PD-1, TIM-3, and LAG-3). The intracellular metabolic changes, altered expression of transcription factors, and a unique epigenetic landscape constitute the exhaustion program. Recently, researchers have made progress in understanding exhausted T cells, with the definition and identification of exhausted T cells changing from phenotype-based to being classified at the transcriptional and epigenetic levels. Recent studies have revealed that exhausted T cells can be separated into two subgroups, namely TCF1+PD-1+ progenitor-like precursor exhausted cells and TCF1-PD-1+ terminally differentiated exhausted T cells. Moreover, the progenitor-like precursor cell population may be a subset of T cells that can respond to immunotherapy.
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