Development and Validation of a Nomogram for Predicting Prognosis to Immune Checkpoint Inhibitors Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy improved the prognosis of patients with non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers are lacking. We explored factors associated with prognosis and developed a predictive model. METHODS: We retrospectively analyzed 130 consecutive stage IIIA-IVB NSCLC patients treated with ICIs combined with chemotherapy. Cox univariate and multivariate proportional hazards regression analyses were used to identify prognostic factors associated with progression-free survival (PFS). A nomogram was developed based on key factors in the training cohort (n = 86) and evaluated in the validation cohort (n = 44). According to the nomogram-based total point scores, we divided patients into low- and high-risk groups. RESULTS: In the training cohort, bone metastases (p = 0.017) and an increased derived neutrophil-to-lymphocyte ratio (p = 0.018) were significantly associated with poor PFS, while smoking (p = 0.007) and programmed death-ligand 1 (PD-L1) ≥50% (p = 0.001) were associated with improved PFS. A nomogram based on these factors was developed to predict PFS at 3, 6, and 12 months. The C-index of the nomogram to predict PFS was 0.725 (95% CI: 0.711-0.739) in the training cohort and 0.688 (95% CI: 0.665-0.711) in the validation cohort. The area under the curve (AUC) exhibited an acceptable discriminative ability, and calibration curves demonstrated a consistency between the actual results and predictions. In the training cohort, the median PFS (mPFS) was 12.3 and 5.7 months in the low- and high-risk groups, respectively (p < 0.001). In the validation cohort, the mPFS was 12.6 and 6.2 months in the low- and high-risk groups, respectively (p = 0.021). CONCLUSIONS: A predictive nomogram was developed to help clinicians assess prognosis early for advanced NSCLC patients who received ICI plus chemotherapy.

Pulmonary sequestration with Aspergillus infection presenting as massive hemoptysis and hemothorax with highly elevated carcinoembryonic antigen in pleural effusion that mimics advanced lung malignancy.

BACKGROUND: Pulmonary sequestration (PS) associated with massive hemoptysis, hemothorax, and elevated tumor markers or even lung malignancy has been reported in several studies. These clinical features combined with lung lesions on chest imaging are sometimes hard to differentiate from lung malignancies and often complicate the diagnostic procedure. CASE PRESENTATION: A 45-year-old man with PS presented with massive hemoptysis, hemothorax, and extremely elevated carcinoembryonic antigen (CEA) in pleural effusion was initially misdiagnosed with advanced lung carcinoma, but was ultimately diagnosed with PS with Aspergillus infection. CONCLUSIONS: PS is rarely concurrent with lung cancer; most of the time, it is misdiagnosed as a malignancy, especially when presenting with a fungal infection, which could remarkably elevate CEA in pleural effusion.

Up-regulated lnc-lung cancer associated transcript 1 enhances cell migration and invasion in breast cancer progression.

Breast cancer remains a leading cause of tumor-related deaths in the world. The pathogenesis contributing to breast cancer progression has not been fully understood. Increasing evidence suggests that long noncoding RNA (lncRNA) is implicated in various kinds of malignant cancers, including breast cancer. In the study, we attempted to explore the expression and effects of lnc-lung cancer associated transcript 1 (LUCAT1) on breast cancer development. Our results indicated that the expression of lnc-LUCAT1 was highly up-regulated in breast cancer tissues and cell lines. Over-expression of lnc-LUCAT1 enhanced cell proliferation, migration and invasion in breast cancer cell lines. Moreover, lnc-LUCAT1 was found to be a target of miR-7-5p. There was a negative correlation between lnc-LUCAT1 and miR-7-5p. The reduction of miR-7-5p was required in the augmentation of breast cancer development induced by lnc-LUCAT1 over-expression. In addition, SOX2 acted as a target of miR-7-5p. SOX2 was an oncogene in breast cancer through promoting cell proliferation, migration and invasion. The in vivo study confirmed the role of lnc-LUCAT1 in promoting tumor growth, accompanied with down-regulated SOX2 expression, whereas up-regulated miR-7-5p. Collectively, the lnc-LUCAT1/miR-7-5p-SOX2 regulatory pathway might provide a new and effective therapeutic strategy to prevent breast cancer development.

High dose of nimustine as an add-on treatment for small cell lung cancer with intracranial metastasis: A case report and literature review.

RATIONALE: Small cell lung cancer (SCLC) characterized by high degree of malignancy and rapid tumor progression. Intracranial metastases often appear at the time of the initial diagnosis or treatment. Besides of radiotherapy, chemotherapy is supposed to have limited effect. PATIENT CONCERNS: A 66-year-old male had blurred vision and unsteady step with moderate headache, nausea, vomit. DIAGNOSES: The patient was diagnosed with SCLC with intracranial metastases. INTERVENTIONS: High dose of nimustine (ACNU) (300 mg/m) add to the regimen containing carboplatin and irinotecan. OUTCOMES: Although the patient suffered severe myelosuppression, the intracranial lesion almost disappeared and maintained half a year. LESSONS: ACNU at a dose of 200 mg/m might be tolerable in combination with other chemotherapeutic drugs for the treatment of SCLC with intracranial metastases besides radiotherapy.

Pulmonary Langerhans Cell Histiocytosis in an Adult Diagnosed with Solitary Inguinal Lymphadenopathy.

We herein report an extremely rare case of pulmonary Langerhans cell histiocytosis with a solitary enlarged inguinal lymph node. A 19-year-old man presented with a non-productive cough lasting for over a five-month period and an enlarged left inguinal lymph node that had persisted for four months. A histopathological study of the lymph node specimens found Langerhans cells coupled with eosinophils. Positive immunohistochemical staining for langerin, Cluster of Differentiation 1a, S100 in the Langerhans cells confirmed the diagnosis, and a mildly impaired ventilation function in addition to multiple peripheral pulmonary cystic lesions were detected. The patient was managed with prednisone (0.5 mg/kg daily), with slow tapering over several months.

FoxP3 genetic variants and risk of non-small cell lung cancer in the Chinese Han population.

CD4(+)CD25(+) regulatory T cell-mediated immunosuppression is one of the crucial mechanisms that tumor cells use to evade the immune system. The forkhead box P3 (FoxP3) gene regulates regulatory T-cell development and function and may modulate the susceptibility to non-small cell lung cancer (NSCLC). Because a single nucleotide polymorphism (SNP) within the FoxP3 gene (rs3761548 in the promoter region) is associated with susceptibility to Graves' disease, this study detected rs3761548 in a hospital-based case-control study. A total of 192 NSCLC patients and 259 healthy subjects were recruited for the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of FoxP3 SNP. The data showed that the A allele of rs3761548 significantly increased NSCLC risk (P=0.000, OR=2.32, 95%CI=1.736-3.102). The AC genotype, AA genotype, and the combined A variant genotype (AA+AC) were also associated with a higher risk of NSCLC (OR [95%CI]=2.147[1.419-3.247], 4.413[2.359-8.255], and 2.563[1.746-3.761], respectively). Moreover, a significantly higher frequency of AA+AC genotype was observed in patients with stage II NSCLC (OR, 2.053; 95%CI, 1.033-4.078). In conclusion, the data from the current study demonstrated for the first time the association of the FoxP3 SNP with a risk of developing NSCLC in the Chinese Han population.

Overexpression of Bcl-2-associated death inhibits A549 cell growth in vitro and in vivo.

The importance of apoptosis during the process of inhibiting tumorigenesis has been recognized. The role of BH3-only proapoptotic protein Bcl-2-associated death (BAD) in tumor growth remains controversial. The aim of this study was to explore the role of BAD in lung cancer cells. Our study showed that expression of BAD was upregulated in A549 cells by a recombinant lentivirus overexpressing BAD. In vitro, BAD overexpression significantly inhibited A549 cell proliferation and induced apoptosis in cell proliferation and apoptosis assays, respectively. The effect of BAD on A549 cells was studied in tumor xenograft of nude mice and the results showed that the tumor volume in the experimental group was smaller than the control groups. Further, immunohistochemical technique was used to determine the cell proliferation and apoptosis status of the lung tumor xenograft cells. This demonstrated that the in vivo and in vitro results were consistent. Taken together, our results indicate that overexpression of BAD inhibits the growth of A549 cells in vitro and in vivo, through inhibiting cell proliferation and inducing apoptosis. Thus, BAD could be a potential therapeutic target.