The preventive role of the red gingeng ginsenoside Rg3 in the treatment of lung tumorigenesis induced by benzo(a)pyrene.

Red ginseng has been used in traditional medicine for centuries in Asia. In this study, we evaluated four types of red ginseng grown in different areas (Chinese red ginseng, Korean red ginseng A, Korean red ginseng B, and Korean red ginseng C) for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene (B(a)P) in A/J mice and found that Korean red ginseng B was the most effective at lowering the tumor load among the four red ginseng varieties. Moreover, we analyzed the levels of various ginsenosides (Rg1, Re, Rc, Rb2, Rb3, Rb1, Rh1, Rd, Rg3, Rh2, F1, Rk1, and Rg5) in four kinds of red ginseng extract and found that Korean red ginseng B had the highest level of ginsenoside Rg3 (G-Rg3), which suggested that G-Rg3 may play an important role in its therapeutic efficacy. This work revealed that the bioavailability of G-Rg3 was relatively poor. However, when G-Rg3 was coadministered with verapamil, a P-glycoprotein inhibitor, the G-Rg3 efflux in Caco-2 cells was lowered, the small intestinal absorption rate of G-Rg3 in the rat models was increased, the concentration levels of G-Rg3 were elevated in the intestine and plasma, and its tumor-preventive abilities in the tumorigenesis rat model induced by B(a)P were also augmented. We also found that G-Rg3 reduced B(a)P-induced cytotoxicity and DNA adduct formation in human lung cells and rescued phase II enzyme expression and activity through Nrf2 pathways, which may be the potential mechanisms underlying the inhibitory effects of G-Rg3 on lung tumorigenesis. Our study showed a potentially vital role of G-Rg3 in targeting lung tumors in murine models. The oral bioavailability of this ginsenoside was augmented by targeting P-glycoprotein, which allowed the molecule to exert its anticancer effects.

Secondary mutant ALK-I1171s in pituitary metastases from a patient with ALK fusion-positive advanced lung adenocarcinoma: A case report and literature review.

Background: Pituitary metastasis accounts for a very low percentage of cases of brain metastasis from lung cancer, and there are uncertainties and challenges in diagnosis and treatment. We hope to shed some light on the diagnosis and treatment by reporting a case of ALK fusion mutation-positive lung cancer pituitary metastasis. Case presentation: We report a 48-year-old female patient with an initial diagnosis of stage IVB lung adenocarcinoma with ALK fusion. The patient developed headache, dizziness, hypopituitarism and hyperprolactinemia one year after treatment with crizotinib. Later, the patient underwent neurosurgical resection of the pituitary tumor and then symptomatic relief. Postoperative pathology suggested pituitary metastasis, and the next-generation gene sequencing conducted on the pituitary metastasis indicated that secondary drug resistance mutation ALK-I1171s occurred after the ALK fusion gene. Conclusion: In this article, we present a patient with suspected pituitary metastases with lung cancer. The progression to pituitary mass resection and next-generation gene sequencing of the pituitary metastasis are suggestive for further diagnosis and treatment.

Intrapleural infusion of tumor cell-derived microparticles packaging methotrexate or saline combined with pemetrexed-cisplatin chemotherapy for the treatment of malignant pleural effusion in advanced non-squamous non-small cell lung cancer: A double-blind, randomized, placebo-controlled study.

Background: Preclincal studies showed the promising efficacy of tumor cell-derived microparticles packaging methotrexate (TMPs-MTX) to treat advanced non-squamous non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). Methods: This randomized, double-blind, placebo-controlled study was conducted at six hospitals in China from 20 July 2015 to 25 April 2019. Patients newly diagnosed with non-squamous NSCLC with MPE were randomly assigned to receive TMPs-MTX (group A) or saline (group B). Patients in both groups received pemetrexed (500 mg/m2 d1) and cisplatin (75 mg/m2 in total for d1-d2). Intrapleural infusion (50 mL saline containing 5 units of TMPs-MTX per perfusion, once every 48 hours, six total perfusions) was initiated on day 5 after pemetrexed-cisplatin chemotherapy. The primary outcome was the objective response rate (ORR) of MPE. Secondary outcomes included the ORR of target lesions, progression-free survival (PFS), overall survival (OS), toxicity, and pleural fluid properties. Results: A total of 86 patients were enrolled in this study and randomly assigned to either group A or group B. Of these, 79 patients were evaluable for response. The ORR of MPE in group A was significantly higher than that in group B (82.50% vs. 58.97%, P = 0.0237). The ORR of target lesions was 25.64% in group A and 20.51% in group B (P = 0.5909), respectively. With a median follow-up time of 18.8 months, median PFS were 6.4 (95% CI, 4.5-12.3) months in group A and 7.3 (95% CI, 6.1-10.4) months in group B (P = 0.6893), and median OS were 19.9 (95% CI, 17.1-28.5) months and 17.5 (95% CI, 11.6-25.0) months (P = 0.4500), respectively. The incidence rates of adverse events were similar in the two groups. The most common treatment-related adverse events were chemotherapy-induced toxicities, including fever, gastrointestinal reactions, hepatic dysfunction, and leukopenia. Conclusion: Intrapleural infusion of TMPs-MTX combined with pemetrexed-cisplatin chemotherapy is safe and effective against MPE in patients with advanced non-squamous NSCLC. Clinical trial registration: http://www.chictr.org.cn (ChiCTR-ICR-15006304).

The effect of combining Endostar with radiotherapy on blood vessels, tumor-associated macrophages, and T cells in brain metastases of Lewis lung cancer.

BACKGROUND: Combining Endostar (ES) with radiotherapy (RT) has shown a promising therapeutic effect on non-small cell lung carcinoma with brain metastases (BMs) in clinical practice. However, the specific mechanism is not yet fully understood. The present study aimed to investigate the effects of ES on blood vessels, tumor-associated macrophages (TAMs), and T cells in a tumor microenvironment treated with RT. METHODS: BM models were established by stereotactic and intracarotid injection of luciferase-Lewis lung cancer (LLC) cells into female C57BL mice. The animals were randomly divided into 4 groups: normal saline (NS), ES, RT, and ES plus radiotherapy (ES + RT) groups. Tumor size was determined with the IVIS imaging system. Tumor specimens were stained with CD34 and α-SMA to investigate tumor vascular changes. The proportions of TAMs, CD4+ T cells, and CD8+ T cells in tumor tissues were determined by flow cytometry and immunofluorescence. The expressions of hypoxia-inducible factor 1α (HIF-1α) and CXCR4 were deduced using western blotting and immunohistochemistry (IHC). RESULTS: ES + RT significantly suppressed tumor growth compared to the other 3 groups. RT decreased M1 and increased M2 in microglial cells and bone marrow-derived macrophages (BMDMs) relative to NS, while ES had the opposite effect. The ratio of CD8+T/CD4+T was increased in the ES + RT group compared to the other 3 groups. Tumor vascular maturity (α-SMA+/CD34+) was increased while HIF-1α was significantly suppressed in the ES + RT group. CXCR4 expression, which is involved in TAM recruitment, increased following RT, whereas, ES attenuated its expression. CONCLUSIONS: Our findings suggest that ES can promote the normalization of tumor blood vessels and increase the anti-tumor immune-related immune cells infiltrating the tumor following RT treatment.

Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients.

RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequent fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET+ patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration, and concomitant EGFR oncogenic alterations were identified in seven patients. Moreover, an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged lung cancers in China. It might be helpful to guide clinicians for more effective personalized diagnostic and therapeutic approaches.

Right atrial epithelioid angiosarcoma with multiple pulmonary metastasis confirmed by multimodality imaging-guided pulmonary biopsy: A case report and literature review.

RATIONALE: Primary cardiac tumors are very rare, and angiosarcoma accounts for about 33% of all primary malignant cardiac tumors. Primary cardiac epithelioid angiosarcoma is a highly aggressive and difficult to diagnose tumor, with early systemic metastasis and poor prognosis. PATIENT CONCERNS: A 35-year-old Han male experienced sudden severe palpitation and moderate dyspnea. The patient received a whole body F-18 fluoro-deoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) scan, the scan showed a large mass in the right atrium (RA) and numerous pulmonary nodules in both lungs. DIAGNOSES: The patient was diagnosed as right atrial epithelioid angiosarcoma with multiple pulmonary metastasis by pulmonary biopsy through CT-guided percutaneous transthoracic fine needle aspiration. INTERVENTIONS: The patient received a cycle of chemotherapy with docetaxel and gemcitabine, followed by another cycle with epirubicin and ifosfamide. OUTCOMES: The chemotherapy was ineffective. After the two cycles, the bilateral pleural effusion steadily increased, the patient had severe dyspnea and palpitation, and died three weeks later, with an overall survival of 2.5 months. LESSONS: Primary angiosarcoma of heart is a very rare and aggressive disease, and its diagnosis and treatment are difficult. Most patients may have systemic metastasis at diagnosis, and have a very short survival without surgical resection. Hence, early diagnosis and surgical resection is extremely important to treat this disease.