Intrapleural perfusion hyperthermia improves the efficiency of anti­PD1 antibody­based therapy for lung adenocarcinoma: A case report.

Chemotherapy based on intrapleural perfusion hyperthermia (IPH) can markedly improve the sensitivity of lung adenocarcinoma cells to anti-programmed cell death receptor 1 (PD1) antibody adjuvant chemotherapy and enhance the clinical response of a patient. In the present study, a unique case of a patient who failed to respond to immunotherapy combined with chemotherapy but achieved prolonged stable disease after treatment with IPH and subsequent sintilimab-based treatment, is reported. A 50-year-old Chinese female patient was admitted to a regional cancer hospital presenting with hemoptysis and persistent fever. The findings of computed tomography imaging and thoracic puncture tissue biopsy indicated a diagnosis of adenocarcinoma. The TNM and clinical stage were identified as cT2N3M0 and stage IIIB, respectively. Immunohistochemical tests showed the expression of programmed death-ligand 1 (PD-L1) with a tumor proportion score of 2%. No other classic genetic alterations were detected. Initially, sintilimab-based chemotherapy at 200 mg was administered, for three cycles from April 2020, and increased pleural effusion was observed on the left side. The best overall response (BOR) assessment of the local lesion was progressive disease. IPH combined with chemotherapy was then carried out from August to September 2020, after which the same course of sintilimab-based chemotherapy as aforementioned was provided from October 2020 to September 2023. The BOR evaluation results during the monotherapy courses were all judged as stable disease. Therefore, it was concluded that IPH can substantially improve the efficiency of anti-PD1 antibody-based therapy for lung adenocarcinoma.

Correlation of magnetic resonance imaging quantitative parameters and apparent diffusion coefficient value with pathological breast cancer.

BACKGROUND: China ranks 120th worldwide for the incidence of breast cancer and 163rd for mortality. Early screening, diagnosis, and timely determination of the optimal treatment plan can help ensure clinical efficacy and prognosis. AIM: To investigate the relationship between quantitative magnetic resonance imaging parameters, apparent diffusion coefficient value, pathological immunohistochemical status, and patient prognosis. METHODS: A total of 108 patients with breast cancer (breast cancer group) and 110 patients with benign breast tumors (benign group) confirmed by pathological examination at our Hospital from September 2013 to August 2016 were selected. All patients had undergone preoperative magnetic resonance imaging (MRI) examinations, and the quantitative parameters of MRI and apparent diffusion coefficient (ADC) values for the two groups were compared. The MRI quantitative parameters and ADC values of patients with different estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor-2 expression were statistically analyzed. The relationship between the quantitative parameters of MRI and ADC values and patient recurrence was analyzed using receiver operating curves. RESULTS: The measured values of the quantitative parameters of MRI- Ktrans, Kep, and Ve in the breast cancer group were higher than those in the benign group; the ADC value in the breast cancer group was lower than that in the benign group, and the difference was statistically significant (P < 0.05). The Ktrans, Ve, and ADC values in patients with ER-positive breast cancer were significantly lower than those in patients with negative ER expression (P < 0.05). After 5 years of follow-up, 22 patients with breast cancer experienced postoperative recurrence. The Kep, Ve, and ADC values of the recurrence group were significantly lower than those of the non-recurrence group, and the difference was statistically significant (P < 0.05). CONCLUSION: MRI quantitative parameters and ADC are related to the expression of breast cancer-related immunological receptor factors and have certain clinical value in assessing postoperative recurrence in patients.

Two case reports of non-small cell lung cancer patients harboring acquired EGFR T790M-cis-C797S benefit from immune checkpoint inhibitor combined with platinum-based doublet chemotherapy.

Background: Acquired resistance is inevitable in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The emergence of EGFR exon 20 C797S is one of the major resistance mechanisms to osimertinib as a third-generation EGFR-TKI. To date, there is no standard of care for NSCLC patients after acquiring EGFR C797S. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various types of cancers in the last decade. Whether NSCLC patients with acquired EGFR C797S could benefit from ICIs remains elusive. Case Description: Herein, we reported two cases of EGFR-mutant NSCLC patients who acquired a tertiary EGFR mutation C797S benefited from ICIs. A 28-year-old woman presented with anepithymia and nausea. Chest computed tomography (CT) revealed a mass in the right lung. She was diagnosed with stage IV lung adenocarcinoma (LUAD) with EGFR exon 19 deletion (19del) based on imaging and next-generation sequencing (NGS) findings. She received icotinib followed by osimertinib, then acquired EGFR T790M-cis-C797S. She had low tumor mutation burden (TMB) and achieved partial response (PR) to a programmed cell death-1 (PD-1) inhibitor sintilimab combined with platinum-based doublet chemotherapy as late-line treatment lasting more than 5 months. A 66-year-old man complained with chest tightness, hemoptysis, and back pain. CT scans revealed a mass in the right lung and metastases to the bilateral lungs, liver, adrenal gland, mediastinal lymph nodes, and bone. He was also diagnosed with EGFR 19del-positive LUAD and treated with icotinib followed by osimertinib. He also acquired EGFR T790M-cis-C797S. The patient had low TMB also and benefited from a PD-1 inhibitor camrelizumab combined with platinum-based doublet chemotherapy as late-line treatment with a progression-free survival (PFS) of 8 months. Two cases had no treatment-related adverse events leading to discontinuation of PD-1 inhibitors. Conclusions: Our study provides the first clinical evidence that ICIs combined with platinum-based doublet chemotherapy may be effective treatment options for overcoming resistance mediated by EGFR T790M-cis-C797S. Clinical trials are needed to evaluate the efficacy and safety of PD-1 inhibitors in the treatment of NSCLC patients harboring EGFR T790M-cis-C797S.

The Effect of the Kirsten Rat Sarcoma Viral Oncogene Homolog (Kras) Proto-Oncogene, GTPase Genetic Polymorphism on the Safety and Efficacy of Bevacizumab Combination Treatment Regimens for Patients with Nonsquamous, Non-Small Cell Lung Cancer with Brain Metastases.

Background: Non-small cell lung cancer with brain metastasis (NSCLCBM) is normally observed in advanced-stage patients. Bevacizumab has shown to improve survival in the first-line treatment of metastatic brain NSCLC when added as a bolus plus irinotecan. However, a better understanding of the molecular mechanism is required to further drive progress in this field. Methods: A total of 155 patients were selected, including 42.10% with Kirsten rat sarcoma viral oncogene homolog (Kras)-mutant tumors. Of the 155 patients, 62.04% had developed brain metastasis (BM). Seven functional single-nucleotide polymorphisms (SNPs) in the Kras gene were extracted from the HapMap SNP database and were used for genotyping. The haplologit command in Statistical Software for Data Science (STATA) was used to model the association between haplotypes and case status. A Cox analysis was used to evaluate the prognostic value of the SNPs. Results: Among the patients treated with combination regimens, recurrence after local treatment was more frequent in those with two types of Kras mutations (odds ratio [OR] = 2.033 [0.5015-4.2552], p = 0.009). Among the patients with untreated BM, overall survival was shorter than that of patients with Kras mutations according to univariate analysis (OR = 5.130 [1.240-41.012], p = 0.033). Conclusions: Kras mutations have a predictive role for BM recurrence and outcome in patients with NSCLC treated with bevacizumab combination regimens.

Elevation of microRNA-365 impedes malignant behaviors of gastric cancer cells by inhibiting PAX6.

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

Durable clinical benefit from afatinib in a lung adenocarcinoma patient with acquired EGFR L718V mutation-mediated resistance towards osimertinib: a case report and literature review.

Osimertinib, as a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), targeting EGFR exon 19 deletions, L858R, and T790M, has shown robust clinical efficacy and promising survival advantages in a subset of non-small cell lung cancer (NSCLC) patients. However, osimertinib-treated patients ultimately develop secondary resistance. Besides EGFR C797S mutation and EGFR amplification, a rare EGFR mutation, L718V, has been reported to confer osimertinib resistance in the literature, which is developed in about 8.0% of osimertinib-resistant NSCLC patients. Although the National Comprehensive Cancer Network or Chinese Society of Clinical Oncology NSCLC guidelines recommend radiotherapy, anti-angiogenesis therapy, chemotherapy and or immunotherapy for the treatment of NSCLC patients who acquire resistance to osimertinib, the feasible treatment options for patients harboring EGFR L718V remain elusive. There is an unmet need to develop effective strategies to treat EGFR L718X-positive NSCLC patients. Herein, we report that a lung adenocarcinoma patient with acquired EGFR L718V mutation-mediated resistance towards osimertinib derived durable response to the second-generation EGFR-TKI afatinib with a progression-free survival of 18 months and counting. Our work provides clinical evidence to administer afatinib in metastatic NSCLC patients who develop EGFR L718V at progression to osimertinib and paves the way for its potential clinical utilization.

LncRNA MCM3AP-AS1 Downregulates LncRNA MEG3 in Triple Negative Breast Cancer to Inhibit the Proliferation of Cancer Cells.

The oncogenic role of lncRNA MCM3AP-AS1 has been reported in several types of cancer, while its role in triple negative breast cancer (TNBC) is unknown. The expression levels of MCM3AP-AS1 and MEG3 in TNBC and paired nontumor tissues from 60 TNBC patients were measured by RT-qPCR. The effects of overexpression of MCM3AP-AS1 and MEG3 on the proliferation of BT-20 and BT-549 cells were evaluated by cell proliferation assay. We found that MCM3AP-AS1 was upregulated in TNBC, while lncRNA MEG3 was downregulated in TNBC, and they were inversely correlated with each other. In addition, the expression levels of MCM3AP-AS1 increased with the increase in tumor size, while the expression levels of MEG3 decreased with the increase in tumor size. In TNBC cells, overexpression of MCM3AP-AS1 led to downregulated expression of MEG3, while overexpression of MEG3 did not affect the expression of MCM3AP-AS1. Cell proliferation analysis showed that overexpression of MCM3AP-AS1 led to increased cell proliferation rate and reduced the inhibitory effects of overexpression of MEG3 on cancer cell proliferation. Therefore, MCM3AP-AS1 downregulates MEG3 in TNBC to inhibit the proliferation of cancer cells.