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PubMed1996

Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases.

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.

Animals↗

PubMed2026

HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the frequently occurring cancers characterized by molecular heterogeneity and multiple immune cell infiltration patterns, which are associated with treatment sensitivity and resistance. However, the specific microenvironmental cells and their mechanisms that lead to treatment resistance in patients need to be explored in greater depth. METHODS: On the basis of patients receiving neoadjuvant therapy in our center, a multicenter, multicohort NSCLC spatial transcriptome, single-cell transcriptome, T-cell receptor repertoire sequencing, bulk RNA transcriptome, phosphorylated proteome, genome mutation, and clinical data were included for a comprehensive assessment of the therapeutic and prognostic impact of HIF1A+ CSF3R+ neutrophils in NSCLC. In vitro experiments validated the functional phenotype of HIF1A+ CSF3R+ neutrophils and co-localization interactions with other cellular subpopulations. Gradient boosting machine (GBM) constructed region of interest (ROI) models for evaluation. Computer-aided drug design (CADD) was used to predict targeted small molecule drugs, and in vivo mouse models were constructed to assess the effectiveness of the combination treatment regimen. RESULTS: Centered on HIF1A+ CSF3R+ neutrophils, recruited exhausted T cells and stromal cells form a hypoxic niche within the tumor region, which was enriched in non-response patients. ROI composed of these specific cellular subpopulations, associated with senescence and glycolysis, accurately predicting NSCLC progression, prognosis, and microenvironment composition. CADD analysis identified that platycodin-D2 specifically targeted CSF3R, reducing HIF1A expression and inhibiting neutrophil activity. Combining navitoclax, platycodin-D2 with anti-programmed cell death protein 1 (PD-1) significantly suppressed tumor proliferation and improved the immunosuppressive microenvironment. CONCLUSION: Our study emphasized the role of HIF1A+ CSF3R+ neutrophils in immunotherapeutic resistance of NSCLC, constructed a microenvironmental immune dysregulation network in a hypoxic ecological niche with HIF1A+ CSF3R+ neutrophils as the center. Platycodin-D2 specifically targeted HIF1A+ CSF3R+ neutrophils, enhancing the efficacy of anti-PD-1 therapy in NSCLC.

Humans↗

PubMed2003

Stromal-derived factor-1alpha/CXCL12-CXCR 4 axis is involved in the dissemination of NSCLC cells into pleural space.

Malignant pleural effusion (PE) is one of the poor prognostic factors in non-small cell lung cancer (NSCLC), and the detailed mechanism of the malignant PE formation is not fully elucidated. Recently, CXCR4, a receptor for chemokine stromal-derived factor-1alpha (SDF-1alpha) that can induce chemotaxis of cells, was reported to be expressed on NSCLC. In this study, we hypothesized that the SDF-1alpha/CXCR4 axis may be involved in the dissemination of malignant cells into pleural space, and investigated its expression, function, and signaling pathway using NSCLC cell lines and clinical samples from 43 patients with NSCLC with malignant PE. We found functional expression of CXCR4 on NSCLC cell lines, and also found that SDF-1alpha could induce migration via phosphatidylinositol 3 (PI-3) kinase- and p44/42 mitogen-activated protein kinase-dependent manner. The SDF-1alpha levels in malignant PE were significantly higher than those in transudate PE and showed a significant positive correlation with PE volumes. The sensitivity and specificity for prediction of recurrence of malignant PE was 61.5% and 83.3%, respectively (cutoff SDF-1alpha = 2,500 ng/ml), and better than those using pH of PE. Cancer cells in malignant PE expressed CXCR4, and mesothelial cells of the pleura stained positive for SDF-1alpha. The SDF-1alpha/CXCR4 axis is involved in the dissemination of NSCLC cells into pleural space.

Aged↗

PubMed2005

Release of bFGF following apoptosis and necrosis in NSCLC cells: effects on chemosensitivity to cisplatin.

The majority of NSCLC cell lines produce elevated levels of bFGF but do not secrete considerable amounts. We therefore investigated the influence of cell death inducing mechanisms on bFGF release. In addition we studied the biological consequences on chemosensitivity of NSCLC cell lines to cisplatin. In our experiment we induced i) apoptosis with cisplatin and ii) necrosis with heat treatment in NSCLC cell lines. Supernatants of apoptotic/necrotic NSCLC cell lines exhibited significantly increased levels of bFGF independent of the cell death inducing mechanism. The incubation of three NSCLC cell lines with these supernatants resulted in enhanced cisplatin-induced apoptosis/necrosis in one of the cell lines (H1299) only. Addition of an anti-bFGF antibody to conditioned supernatant of H1299 cells abolished this effect partially. These results suggest that the release of bFGF following cell death contributes to enhanced chemosensitivity in NSCLC cell lines.

Antibodies, Monoclonal↗

PubMed2006

High rate of molecular alteration in histologically tumour-free bronchial epithelium of NSCLC patients detected by multicolour fluorescence in situ hybridisation.

Detection of molecular abnormalities could provide an essential tool for the diagnosis of non-small cell lung cancer (NSCLC) and defining patients at risk for early relapse. Fluorescence in situ hybridisation (FISH) targeting 17 gene loci was applied to determine the frequency of molecular alteration in NSCLC probes and adjacent tumour-free bronchial epithelium. FISH was performed on fresh frozen specimens from 76 patients with histologically confirmed NSCLC and 54 specimens of adjacent tumour-free tissue. Routine autopsy lung tissue probes from 7 cancer-free patients served as a control group. Locus-specific (3p14.2, 3p21.2, 3p21.3, 3p25.3, 5p15.2, 7p12, 8q24.12, 9p21, 13q14, and 17p13.1) as well as centromere probes (4, 6, 7, 9, 11 and 16) were used. Molecular alterations using FISH on interphase nuclei were detected in 100% of NSCLC tumour specimens and 89% of microscopically tumour-free tissues of NSCLC patients. In histologically 'normal' epithelium, the most frequent alterations were seen with locus-specific probes for 3p14.2, 3p.21, 3p21.3, 3p25.3 and 7p12 and centromere-specific probes 11 and 16 (12-93%). As expected, the majority of genetic alterations seen in 'premalignant' specimens were found in the correlating tumour probes. None of the tested parameters revealed prognostic significance in univariate Cox analysis. FISH analysis, performing multicolour strategies, demonstrated its power in detecting genetic abnormalities in NSCLC specimens and even in tumour-free sections of tumour patients.

Adult↗

PubMed2005

The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel.

The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC.

Angiogenesis Inhibitors↗

PubMed2005

An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth in integrin alpha1-null mice.

The role of matrix metalloproteinase (MMP)9 in lung cancer progression is controversial. MMP9 promotes local tumor progression and distant metastasis in mouse models by enhancing extracellular matrix degradation, releasing VEGF from extracellular matrix and promoting vascular pericyte recruitment. Furthermore, increased plasma MMP9 expression levels in human subjects with metastatic non-small cell lung cancer (NSCLC) inversely correlates with survival. In contrast, MMP9 can benefit the host by generating inhibitors of endothelial cell proliferation such as angiostatin and NC1 domains of collagen IV. To better understand the role of host MMP9 on the primary growth and metastatic potential of NSCLC, we performed an orthotopic model of NSLC in integrin alpha1-null mice (a genetic model for increased MMP9). In these mice we observed decreased number, size and vascularization of primary NSCLC tumors when compared to wild type controls. In addition, decreased number and size of NSCLC-derived metastases were evident in the alpha1-null mice. Furthermore, pharmacological inhibition of MMPs in the alpha1-null mice at the time of tumor cell injection resulted in an increase in the number of both primary and metastatic lung cancer as compared to untreated mice, suggesting that primary growth and metastases of NSCLC are worsened by the early inhibition of MMPs. In conclusion, although MMP9 may potentially promote tumor growth and metastasis, production of MMP-dependent anti-angiogenic factors seems to override these effects and protects the host from NSCL growth and progression.

Animals↗

PubMed1998

Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE-binding activity and recruitment of specific AP-1 proteins.

Transitions from small cell (SCLC) to non-small cell lung cancer (NSCLC) cells have been documented both in vitro and in vivo and are thought to be an important step during tumor progression of human small cell lung cancer towards a treatment-resistant tumor state. We have screened NSCLC and SCLC cell lines for differences in the composition of nuclear transcription factors using consensus oligonucleotide sequences (SRE, Ets, TRE, CRE, B-motif, GAS, E-box). We found NSCLC cells to exhibit significantly higher AP-1 binding activity than SCLC cells consistent with the increased expression of CD44, an AP-1 target gene. To gain more insight into the molecular mechanisms underlying these differences, we analysed SCLC cell lines (NCI-N592 and NCI-H69) which were phenotypically transformed into NSCLC-type cells by transfection with activated H-ras and c-myc oncogenes. In these cells, ras-induced transition is accompanied by a strong induction of AP-1-binding activity along with increased expression of CD44 mRNA and protein. When analysing the composition of the AP-1 complex in more detail and comparing ras-induced versus phorbol ester-induced changes, we found Fra-1 to be the major component induced in ras-transfected but not in phorbol-ester treated or non-treated parental SCLC cells. This finding is paralleled by the observation that among the various members of the Fos and Jun family analysed (c-Fos, FosB, Fra-1, Fra-2, c-Jun, JunD, JunB) fra-1 is the only gene to be exclusively expressed in NSCLC cells but not in cells of SCLC origin. Our data, thus, point to a histiotype-related mechanism of recruitment among AP-1 proteins which may have bearings on the fate of lung cancer development.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Heterogeneity of stage IIIA non-small cell lung cancers (NSCLC) and evaluation of late results of surgical treatment.

AIMS: The aim of the study was assessment of the heterogeneity of stage IIIA non-small cell lung cancers (NSCLC) and the late results of surgical treatment. METHODS: The study group consisted of 83 consecutive patients discharged between 1988 and 1992 undergoing radical operative treatment for stage IIIA NSCLC. Squamous cell carcinoma was diagnosed in 54 (65.1%) patients, adenocarcinoma in 23 (27.7%), large cell carcinoma in 2 (2.4%) and mixed (i.e. adenoid-squamous type) in 4 (4.8%). In respect of pTNM staging, 19 (22.9%) patients had T3N1M0, 35 (42.2%) had T2N2M0 and 29 (34.9%) had T3N2M0. RESULTS: Overall, 13.3% of patients with stage IIIA NSCLC survived 5 years following the operation and 8.7% survived 10 years. Analysis of follow-up study indicated that this group was heterogenic. In T3N1M0 group 26.3% survived 5 years following the operation, in T2N2M0 group 14.3%, in T3N2M0 group 3.5% (P = 0.015). Of 23 patients with N2 disease and no metastases in hilar lymph nodes ('skip' metastases), 26.1% survived 5 years, whereas none of 41 patients with metastases spreading by continuity survived (P = 0.0015). If mediastinal lymph node metastases were diagnosed in one level, 25% patients survived 5 years, but if two or more levels were affected, 2.3% only (P = 0.0214): 85.7% of patients with well-differentiated (G1) cancer survived 5 years and 62.0% 10 years, whereas among those with moderately differentiated (G2) tumours, 11.8% and 8.8%, respectively. No patient survived 5 years after resection of poorly differentiated (G3) cancer (P < 0.001). CONCLUSIONS: (1) Patients operated for stage IIIA NSCLC are a heterogeneous group, which makes it difficult to predict late results. (2) Patients operated for stage IIIA NSCLC have a better prognosis if metastases are discovered in level one mediastinal lymph nodes, particularly in the superior part of mediastinum, or if 'skip' metastases (pulmonary hilus unaffected) are discovered, as compared to those with N2 disease. (3) Poor histologic differentiation of the tumour is a bad prognostic factor.

Adenocarcinoma↗

PubMed2003

Growth and functional reactivity of lymphocytes obtained from three anatomic compartments in patients with non-small-cell lung cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) claims the lives of both men and women worldwide. In this study, we describe the ability to expand lymphocytes from solid tumor biopsies, pleural fluid, and peripheral blood of patients with NSCLC. While lymphocytes readily expanded from both solid biopsies and pleural fluids, the incidence of obtaining tumor-specific lymphocytes was low. Specific cytolytic and/or cytokine-releasing activity was observed in tumor-infiltrating lymphocytes (TIL) from 3/15 solid tumor biopsies (20%) and 2 of 4 pleural fluid samples (50%). Two of the CTL derived from solid tumor were cytolytic, one being HLA-A2 restricted while the other was either restricted at HLA-A30 or - B18. One of the pleural fluid cytotoxic T lymphocyte (CTL) was also HLA-A2 restricted. Peripheral blood from NSCLC patients was studied using mixed lymphocyte tumor cell cultures (MLTC) as reported previously. Peripheral blood lymphocytes were cultured with allogeneic NSCLC-TC line 29.7, which expressed by gene transfer the lymphocyte costimulatory molecule CD80. Of 9 HLA-A2 patient samples tested, 8 gave rise to lymphocytes, which lysed NSCLC tumor cells expressing HLA-A2 in an major histocompatibility complex (MHC)-restricted fashion. While specific CTL can be generated from all anatomic sites, for clinical trials peripheral blood appears to be the site of choice for obtaining specific precursors.

Biopsy↗

PubMed2006

Chemotherapy of advanced NSCLC in special patient population.

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial. The best treatment for elderly patients with advanced NSCLC is still debated. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, the role of platin-based chemotherapy needs to be defined in prospective randomised trials. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Also for PS2 patients there is no consensus on standard treatment. On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations and role of new targeted therapies.

Aged↗

PubMed2006

Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.

OBJECTIVES: We investigated the role of cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cachexia development in newly diagnosed nonsmall cell lung cancer (NSCLC) patients. METHODS: : We evaluated 44 (M/F:41/3) NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a weight loss of > or =10% consisted the cachectic group (n:23, M/F:21/2) and the ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2). RESULTS: Body mass index (BMI) of cachectics was significantly lower than that of noncachectics (21.0 +/- 2.9 versus 24.5 +/- 3.6, P = 0.02) and controls (21.0 +/- 2.9 versus 25.5 +/- 2.6, P = 0.01). Serum TNF-alpha level did not differ between cachectic and noncachectics (37.3 +/- 39.1 and 51.6 +/- 84.2 pg/mL, respectively). However, it was significantly higher in NSCLC patients compared with controls (44.1 +/- 64.3 and 15.1 +/- 14.3 pg/mL, P = 0.03). Serum IL-6 level was not different between 3 groups (6.4 +/- 4.1, 8.9 +/- 16.3, and 4.1 +/- 3.5 pg/mL, respectively) but it correlated significantly with TNF-alpha (r = 0.4, P = 0.006) and BMI (r = -0.3, P = 0.03). Erythrocyte sedimentation rate (ESR) correlated significantly with TNF-alpha (r = 0.4, P = 0.003) and BMI (r = -0.3, P = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in cachectics and noncachectics, with no statistical difference (12.2 +/- 3.7 and 11.2 +/- 1.0 months, respectively). CONCLUSIONS: TNF-alpha and IL-6 levels did not differ significantly between cachectics and noncachectics. However, significant correlations between IL-6, BMI, and TNF-alpha suggested that these cytokines acted as cofactors in weight loss. Survival was neither influenced by BMI, nor the cytokine levels in the present study. The significant correlation of ESR with TNF-alpha suggested that ESR could provide valuable clue for considerable weight loss in the follow-up of NSCLC patients.

Aged↗

PubMed2005

Clinical benefit in NSCLC: advanced-stage patients require symptom-improving palliation. Experiences from the 'Iressa' expanded access program.

BACKGROUND: The molecular genesis of lung cancer and its treatment remain hot spots of medical research because of the high mortality rates especially associated with non-small-cell lung cancer (NSCLC). New agents are required. The epidermal growth factor receptor (EGFR) pathway inhibitor gefitinib (Iressa) has been the first approved drug for NSCLC within this new therapeutic class. PATIENTS AND METHODS: The anti-tumor activity of gefitinib in a monocentric and prospective case series of 72 patients with refractory NSCLC is analyzed. Patients who had histologically confirmed NSCLC with one or more previous chemotherapies were eligible for enrollment. Patients received 250 mg gefitinib orally once daily for at least 28 days. RESULTS: An 8% response rate (PR) and an additional 42% rate of disease stabilizations (SD) have been found in our patient collective. The median survival of all patients was 8.6 weeks (95% CI 5.9-11.2). Comparing responders, patients with stable disease, and progressive patients it becomes evident that patients sensitive to gefitinib get a clinical benefit in terms of palliation and overall survival. Adenocarcinoma histology and former nicotine abstention seem to favor sensitivity to gefitinib. CTC grade 3/4 toxicities were observed in only one patient in form of skin reactions. Mild toxicities (CTC grade 1/2) were diarrhea, conjunctivitis and elevation of transaminases. CONCLUSION: These prospective data suggest an activity of gefitinib in pre-treated NSCLC patients without relevant toxicities. They are in agreement with other published data.

Administration, Oral↗

PubMed2004

Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis.

BACKGROUND: The Duffy antigen receptor for chemokines (DARC) is known to be a promiscuous chemokine receptor that binds a variety of CXC and CC chemokines in the absence of any detectable signal transduction events. Within the CXC group of chemokines, DARC binds the angiogenic CXC chemokines including IL-8 (CXCL8), GROalpha (CXCL1) and ENA-78 (CXCL5), all of which have previously been shown to be important in non-small cell lung carcinoma (NSCLC) tumor growth. We hypothesized that overexpression of DARC by a NSCLC tumor cell line would result in the binding of the angiogenic ELR+ CXC chemokines by the tumor cells themselves, and thus interfere with the stimulation of endothelial cells and induction of angiogenesis by the tumor cell-derived angiogenic chemokines. RESULTS: NSCLC tumor cells that constitutively expressed DARC were generated and their growth characteristics were compared to control transfected cells in vitro and in vivo in SCID animals. We found that tumors derived from DARC-expressing cells were significantly larger in size than tumors derived from control-transfected cells. However, upon histological examination we found that DARC-expressing tumors had significantly more necrosis and decreased tumor cellularity, as compared to control tumors. Expression of DARC by NSCLC cells was also associated with a decrease in tumor-associated vasculature and a reduction in metastatic potential. CONCLUSIONS: The expression of DARC in the context of NSCLC tumors may act as a chemokine decoy receptor and interferes with normal tumor growth and chemokine-induced tumor neovascularization.

Animals↗

PubMed2025

USP2 reversed cisplatin resistance through p53-mediated ferroptosis in NSCLC.

BACKGROUND: It has demonstrated the indispensable role of ferroptosis in conferring cisplatin resistance in non-small cell lung cancer (NSCLC), as well as the involvement of ubiquitin-specific protease (USP) in regulating ferroptosis. This paper aspired to the mechanism of USP2 and ferroptosis on NSCLC cisplatin resistance. METHODS: Ubiquitin-specific protease mRNA expression, was detected through RT-qPCR. In vitro functional assays assessed the effects of USP2 overexpression on DDP resistance, cell proliferation capability, and ferroptosis markers in A549/DDP and H1299/DDP cells. Ubiquitination assays evaluated the ubiquitination levels of p53 following USP2 overexpression. Co-immunoprecipitation (Co-IP) assays confirmed the binding relationship between USP2 and p53. In vivo experiments in mice explored the specific role of the USP2-p53 axis in a xenograft tumor model. RESULTS: USP2 expression was suppressed in cisplatin-resistant NSCLC cells. USP2 overexpression inhibited cell viability in cisplatin-resistant cells. Among the ferroptosis markers, the results showed that USP2 overexpression promoted LDH release, Fe2+ level, MDA and Lipid ROS, while inhibited GPX4 activity and GSH levels. The WB results revealed that USP2 overexpression inhibited GPX4, SLC7A11 and cytoplasm p53 protein expression, while promoted the nucleus p53 protein expression. Moreover, USP2 directly bound to p53 and USP2 overexpression stabilized p53 protein by suppressing its ubiquitination. In vivo experiments further suggest that the USP2-p53 pathway plays a crucial role in regulating cisplatin sensitivity in A549/DDP cells. CONCLUSION: USP2 acted on the K305R site of p53, which resulted in its deubiquitination. This cellular process could modulate cisplatin resistance through ferroptosis in NSCLC. This study could provide a potential therapeutic target to NSCLC.

Ferroptosis↗

PubMed1999

[Gemcitabine hydrochloride is a new anti-cancer agent which will be available in the patients with non-small cell lung cancer (NSCLC) in Japan].

Gemcitabine hydrochloride is a novel anti-cancer drug which is marketed as an indication for non-small cell lung cancer (NSCLC). This drug is already on the market and has been done many clinical trials. In order to evaluate its efficacy in treating NSCLC, many studies of gemcitabine by combination chemotherapy using agents such as cisplatin, which is a key drug in treating NSCLC, and paclitaxel, docetaxel and vinorelbine, which are novel anti cancer agents, were conducted. Although the efficacy of this drug was confirmed in terms of the combination therapy from the results, the optimal dosage schedule of this drug was not established because each study showed a different result in terms of the dosage as well as the dosage interval, thus, it is necessary to discuss and establish the optimal dosage schedule. Also comparative studies between the single therapy of gemcitabine and the existing combination therapy were conducted and it was reported that the single therapy was as effective as the conventional combination therapy. Based upon the results, it is considered that gemcitabine is a potential option in the chemotherapy for NSCLC. Gemcitabine has been already approved as indications for NSCLC as well as pancreatic cancer abroad and now there have been discussions on its efficacy against other kinds of cancer such as breast cancer. Clinical trials in order to evaluate its efficacy for pancreatic cancer have been conducted here in Japan and it is also expected to expand develop the efficacy against other kinds of cancer.

Adult↗

PubMedDate not supplied

Tumor size does not have prognostic significance in stage Ia NSCLC.

PURPOSE: We aimed to determine whether the prognosis of non-small cell lung cancer (NSCLC), with lesions 2 cm or less in diameter, was better than that of Stage Ia lung cancer having a diameter of more than 2 cm. METHODS: We reviewed 64 cases of NSCLC which were preoperatively diagnosed as TINOMO. The tumors were classified into 2 groups on the basis of a tumor diameter set at 2 cm. After comparison of background factors, we compared the prognoses of the groups and determined the prognostic factors in Stage IA NSCLC. RESULTS: No differences were observed in the survival rate between the 2 groups. Statistically significant factors for the survival period in Stage IA NSCLC were serum carcino-embryonic antigen (CEA), residual tumor condition and lymph node metastasis. Those cases where CEA was abnormal were all in Stage II or inllmore advanced stage. CONCLUSION: It is not justifiable to sub-classify Stage IA NSCLC on the basis of a tumor diameter of 2 cm. The present study revealed that the most important preoperative prognostic factor was serum CEA.

Adenocarcinoma↗

PubMed2000

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer (NSCLC)--is there a role for a new chemotherapy programme?

Phase II with single-agent docetaxel, in second-line NSCLC, demonstrated an overall response rate of 20%, with a median response duration of 7 months and a median survival time of 9 months. These results suggested that docetaxel had promising activity in patients with platinum-resistant or refractory NSCLC. Phase III studies in this patient population subsequently confirmed this activity; docetaxel prolonged survival when compared to either vinorelbine/ifosfamide or the best supportive care. The phase II studies with docetaxel in first-line NSCLC produced an overall response rate of 30% in evaluable patients, with a median response duration of 6 months and a median survival time of 9 months. A phase III randomized study demonstrated a significant improvement in survival and time to progression with docetaxel, compared to the best supportive care. Based on the activity observed with single-agent docetaxel, combination and multimodality studies with docetaxel have also been conducted. Docetaxel is an active agent in first- and second-line NSCLC. Ongoing studies in the front-line treatment of NSCLC will further define the role of docetaxel in the neo-adjuvant setting.

Antineoplastic Agents, Phytogenic↗