Quantification of circulating endothelial cells as a predictor of response to chemotherapy with platinum and pemetrexed in patients with advanced non-squamous non-small cell lung carcinoma

Small cell lung carcinoma (SCLC) frequently metastasizes early in the course of the disease. P-selectin (P-sel), a cell adhesion molecule expressed on activated platelets and endothelial cells (EC), has previously been demonstrated to mediate binding of platelets to SCLC. We hypothesized that P-sel facilitates attachment of SCLC to EC, acting as an important factor in SCLC metastasis. To test this hypothesis, attachment of H82 cells (SCLC cell line) to EC was quantified. Attachment of H82 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated EC was increased compared with control EC. Increased attachment of H82 cells to EC was apparent after 10 min of TPA activation, reached a peak after 30 min, and returned to baseline after 120 min of exposure. The TPA-induced increase in H82 cell attachment to EC was inhibited by addition of anti-P-sel antibodies but not by addition of anti-E-selectin antibodies. The TPA-induced increase in H82 cell attachment was likely mediated by activation of EC protein kinase C (PKC). Pretreatment of the EC with PKC inhibitors effectively blocked the TPA-mediated increase in H82 cell attachment. In addition, prolonged exposure of EC to TPA resulted in decreased expression of the PKC-alpha and PKC-epsilon isoforms. These data indicate for the first time that attachment of SCLC to activated EC appears to be mediated by increased expression of P-sel on the EC surface, which may result from activation of specific isoforms of PKC.

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Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9061 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9061-9061 ◽

Cited By ~ 4

Author(s):

Jules Derks ◽

Noémie Leblay ◽

Robert Jan van Suylen ◽

Erik Thunnissen ◽

Michael den Bakker ◽

...

Keyword(s):

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Stage Iv ◽

Progression Free Survival ◽

Large Cell ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Netherlands Cancer Registry ◽

Response To Chemotherapy

9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype(wt)) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation(mt) in TP53 was present in 87%, RB1mt in 46%, STK11mt in 13% and KEAP1mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11mt (100%) but not KEAP1mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1wt, NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.

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ICAM-1 supports adhesion of human small-cell lung carcinoma to endothelial cells

Clinical & Experimental Metastasis ◽

10.1023/b:clin.0000037696.36108.27 ◽

2004 ◽

Vol 21 (3) ◽

pp. 185-189 ◽

Cited By ~ 17

Author(s):

Angela H. Finzel ◽

Armin J. Reininger ◽

Patrick A. Bode ◽

Laurenz J. Wurzinger

Keyword(s):

Endothelial Cells ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma

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Clinical response to chemotherapy in non-small cell lung carcinoma patients

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20195531 ◽

2019 ◽

Vol 7 (12) ◽

pp. 4641

Author(s):

Ravi Kiran Narukurthi ◽

Nallamothu Murali Krishna ◽

Jetty Mounika ◽

T. Jaya Chandra

Keyword(s):

Partial Response ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Stage Iv ◽

Small Cell ◽

Stage Iii ◽

Clinical Staging ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Response To Chemotherapy

Background: Lung carcinoma is the most common. With this, a study was conducted to assess the clinical profile of Non-small cell lung carcinoma (NSCLC) and also to evaluate the response to chemotherapy in various stages of NSCLC.Methods: It was a prospective study. All the clinically confirmed cases with NSCLC were taken into consideration. Clinical staging was done, diagnosis was confirmed by histopathological findings. Treatment was given depending on the stage of carcinoma. Patients were evaluated before each cycle of chemotherapy for any progression of disease. Pathological response was evaluated after completion of 6 cycles of chemotherapy. Chi square test was used to find the statistical significance; p<0.05 was considered statistically significant.Results: Total 153 patients admitted to oncology wing were taken to the study, with mean age 59.07±10.618 years, 2.6 male female ratio. In this 73% were in stage III and the remaining in stage IV NSCLC. Majority (56.10%) of the study subjects in stage III NSCLC showed partial response, Majority (68%) of the subjects in stage IV NSCLC showed partial response; the difference was Statistically significant (p<0.05).Conclusions: NSCLS is common in older people with male dominance due to habits.

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