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Oligometastasis is an intermediate status between the locally advanced and wide spread disease. Patients with oligometastasis may obtain long-term survival after local treatment. Stereotactic body radiation therapy (SBRT) can deliver radical ablative doses in a small number of fractions, which is a highly precise local ablation therapy. Approximately half of patients diagnosed with colorectal cancer (CRC) will develop metastases, with the liver and lung as the most common site of involvement. In this article, the safety, local efficacy and prognostic factors of SBRT for liver and lung oligometastases from CRC were illustrated. The highlights of SBRT implementation were also discussed. SBRT is safe and effective for oligometastases from CRC under respiratory motion management and robust quality assurance.
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In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.
Subject(s)
Animals , Mice , Rats , Cyclooctanes , Lignans , Lipids , Lung Neoplasms/drug therapy , Nanoparticles , Polycyclic Compounds , Polyethylenes , Polymers , Polypropylenes , SwineABSTRACT
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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Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.
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Las metástasis sintomáticas al colon de un carcinoma de pulmón son raras, a pesar de ser una neoplasia que representa el 12,9% de la incidencia mundial de cáncer. El colon es un sitio infrecuente de metástasis, con una prevalencia reportada menor al 0,5% en pacientes con carcinomas de pulmón, existiendo en la literatura mundial pocos casos. Es inusual que sea la forma de presentación de este tipo de neoplasia. Con respecto a las manifestaciones clínicas que se reportan pueden cursar con obstrucción intestinal como síntoma cardinal. Se presenta el caso de un paciente que curso con hemorragia de vías digestivas bajas como manifestación inicial de múltiples lesiones metastásicas a colon de un carcinoma de pulmón de célula no pequeña.
The symptomatic metastasis of the colon from a pulmonary cancer is rare; however, the global incidence of pulmonary cancer is 12.9%. It is an infrequent site of metastasis, with a prevalence of less than 0.5% in patients with pulmonary cancer. One of the most common manifestation is intestinal obstruction. We present a case report of a patient with an acute lower intestinal bleeding from multiple metastasis lesion of the colon as the initial manifestation of a non-small cell lung carcinoma.
Subject(s)
Aged , Humans , Male , Colonic Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Colonic Neoplasms/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosisABSTRACT
Targeted therapeutic drug,having such advantages as targeting,safety,convenience,etc,is increasingly favored by non-small cell lung cancer (NSCLC) patients.At present,there are many kinds of molecular targeted drugs used in clinic,and remarkable efficacy was achieved,and the pain caused by conventional chemotherapy was avoided.At the same time,with the deepening of the understanding of the mechanism of tumor immune,new targeted drugs will also continue to be developed.The emergence of the third generation EGFR-TKI brings new hope for first generation EGFR-TKI resistant patients.Combined use of different immune therapeutic agents,combined application of immunotherapy drugs and cytotoxic chemotherapy drugs and radiotherapy,and the exploration of its predictive biomarkers will become a hot spot in the research of lung cancer.This will undoubtedly bring a new dawn for the treatment of NSCLC.Based on the domestic and foreign research literatures and related materials,this article reviews the latest research progress of various molecular targeted drugs for treatment of NSCLC.
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Objective To study the inhibitory effect of curcumin on the proliferation,migration and invasion of non-small cell lung cancer cell A549,and to discuss further if it is closely related to the expression of c-Jun N-terminal kinase (JNK) and relative protein p38.Methods A549 cells were cultured by conventional method,and then treated with different concentration of curcumin (10,20,40,80 μmol · L-1).The proliferation,migration and invasion of A549 cells were measured by real-time cellular analysis (RTCA).The expression levels of JNK,p-JNK,p38 and P-p38 were detected by real-time PCR and Western blotting.Results Curcumin showed an antiproliferation effect against A549 cells with IC50 =40 μmol · L-1,and curcumin exhibited obviously inhibitory effect on the migration and invasion of A549 cells.Additionally,compared with control group,curcumin suppressed the expression of JNK and p38 at the gene level,and significantly inhibited the expression of JNK,P-JNK,p38 and p38 (P＜0.05) at the protein level.Conclusion These results demonstrated that curcumin can inhibit the proliferation,migration and invasion of A549 cells via reducing the level of JNK,p38 phosphorylation,and blocking JNK signal transduction pathway.
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Objective To observe the effect of apatinib on the invasion ability and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cell line A549 and H460.Methods Different doses of apatinib were incubated with the A549 and H460 cells,then the effect of apatinib on the invasion of A549 cells was detected by Transwell assay,and the change of cell morphology was observed by optical microscope,and the expression of EMT related proteins were detected by Western blotting.Results The cell viability of A549 and H460 have no change when the concentration of apatinib was under 120 nmol·L-1.Therefore,60 nmol·L-1 and 120 nmol·L-1 apatinib were used in the further experiments.The invasion of A549 cells was reduced after apatinib incubation for 48 h,with cell morphology changes,and the expression of E-cadherin was enhanced,with the depresion of N-cadherin,Vimentin and Snail,which were related to the progress of EMT.Conclusion Apatinib could induce the MET,and reduce the invasion ability of A549 and H460 cells.
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Objective To determine the effect of apigenin on inducing apoptosis and inhibiting proliferation of non-small cell lung cancer cell line NCI-H1650. Methods NCI-H1650 cell line was cultured routinely in vitro, with blank control group and different concentrations of apigenin (10, 20, 40, 80 μmol?L-1). The blank control group was RPMI-1640 solution without apigenin. Cell proliferation was detected by MTT. Hoechst 33258 was applied to observe morphological changes of the apoptotic cells after treatment of different concentrations of apigenin. Flow cytometry AnnexinV-FITC/PI double staining method was used to determine cell apoptosis rate. The expression levels of apoptosis-related signaling molecules Bax and Bcl-2 protein were performed by Western blotting. Results MTT showed that apigenin inhibited proliferation of NCI-H1650 cell line in a concentration-and time-dependent manner (P<0.01).Hoechst 33258 nuclear staining showed typical characteristics of apoptosis in certain concentration-dependent manner, such as nuclear condensation and appearance of apoptotic bodies. In addition, the results of flow cytometry staining indicated that the apoptotic rate of NCI-H1650 cells cultured with blank control group and different concentrations of apigenin (10, 20, 40, 80 μmol?L-1) for 48 h was (5.00±0.33)%, (18.05±4.67)%, (21.48± 1.95)%, (43.24±1.11)%, (66.23±3.65)%, respectively (P<0.01).Western blotting results showed that the expression levels of Bax increased with increasing of the drug concentration, but Bcl-2 decreased with increasing of the drug concentration. Conclusion Apigenin can inhibit the proliferation and induce apoptosis of NCI-H1650 cells in non-small cell lung cancer. Mechanisms may be related to increase of the expression of apoptosis related protein Bax and decrease of the expression of anti apoptosis protein Bcl-2.
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Objective To explore the pharmaceutical care approaches for patients with lung cancer complicated with renal insufficiency receiving pemetrexed chemotherapy. Methods An elderly patient with lung cancer complicated with renal insufficiency receiving pemetrexed chemotherapy faced inevitable safety risks.Clinical pharmacists considered it as an intervention point, and provided individual pharmaceutical care. Results Clinical pharmacists fully assessed the safety risks of the case receiving pemetrexed chemotherapy with clinicians, assisted in improving the therapeutic regimen, and carried out medication education for the patient. No serious adverse drug reactions occurred in the patient, and anti-tumor efficacy was obtained. Conclusion For patients of lung cancer complicated with renal insufficiency receiving pemetrexed chemotherapy, clinical pharmacists should focus on creatinine clearance rate, and decide whether the combined use of platinum anti-tumor drugs, non steroidal anti-inflammatory drugs and zoledronic acid can be adopted, and follow-up on adverse drug reactions and anti-tumor efficacy.
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Objective To investigate the inhibition mechanism of tetramethylpyrazine combined with cisplatin on angiogenesis in Lewis lung cancer mice and to observe the mechanism of Arresten on angiogenesis in lung cancer. Methods The model of Lewis lung adenocarcinoma mouse xenograft was established in this work, and 40 mice were randomly divided into 4 groups: 0.9% sodium chloride solution group(NS group), tetramethylpyrazine group(TMP group), cisplatin group(DDP group), tetramethylpyrazine plus cisplatin group(TMP + DDP group), 10 mice in each group.Mice in NS group were given 0.2 mL of 0.9% sodium chloride solution, mice in DDP group were given 0.2 mL of 2 mg.kg-1 of cisplatin, mice in TMP group were given 0.2 mL of 100 mg.kg-1 of tetramethylpyrazine, mice in TMP+DDP group were given 2 mg.kg-1 of cisplatin and 100 mg.kg-1 of tetramethylpyrazine, each 0.1 mL .Tumor size was measured every day to calculate the tumor volume.The mice were sacrificed to stripp the subcutaneous tumor after continuous medication. The expressions of Arresten, integrin α1β1 and VEGF were determinated by immunhistochemistry and Western blotting. Results The tumor growth of NS group was the fastest and TMP+DDP group was the slowest. Compared with NS group, the expression of Arresten in the other three groups was increased( P<0.01) , and the TMP+DDP group exhibited the highest expression;at the same time, integrin α1β1 , VEGF in the other three groups was decreased(P<0.01), and the TMP+DDP group exhibited the lowest expression.The expression of integrinα1β1 and VEGF was negatively related to Arresten, and the expression of integrin α1β1 was positively correlated with VEGF. Conclusion TMP can inhibited the growth of Lewis lung carcinoma and angiogenesis. Moreover, in combination with cisplatin, TMP can also improved the effect of chemotherapy and then the survival state of mice. The mechanism of action, which TMP suppress tumor angiogenesis may be through improving Arresten and inhibiting integrin α1β1 and VEGF. And the action mechanism of Arresten may be implemented by inhibiting the expression of VEGF by incorporation with integrinα1β1 or by itself to inhibit the expression of VEGF.
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Objective To observe the effect of paclitaxel long-circulating thermo-sensitive liposome ( PLTL) on inhibiting the growth of transplanting Lewis lung cancer cells in C57BL/ 6 mice. Methods The model of mice carried Lewis lung cancer was established. 40 tumor-bearing mice were divided into five groups randomly: blank control group, model control group, PTX group, PTL group and PLTL group, 8 mice for each group. The blank control group and the model control group were injected with 0. 9% sodium chloride solution. In PTX group, PTL group and PLTL group, the dose of per injection was calculated with the reference of PTX for 20 mg·kg-1 , diluted with 0. 9% sodium chloride solution, and the mice were injected via the tail vein with a volume of 0. 2 mL each time. Except for the blank control group, 5 minutes after administration, the tumors of the other groups were subjected to local hyperthermia at (42±0. 5) ℃ for 30 min. During the treatment period, transplantation tumor growth was observed; pathological morphology changes of tumor tissues and cells were detected by HE stain; apoptosis rate of tumor cells was determined by flow cytometry to investigate the inhibition effect of PLTL combined with local thermal therapy on the tumor. Results The inhibition rate of tumor in model control group, PTX group, PTL group and PLTL group was 21. 81% , 48. 87% , 57. 22% and 78. 87% , respectively. The apoptosis rate of tumor cells was (20. 4 ± 4. 2)% , (42. 7 ± 3. 8)% , (54. 6±2. 9)% and (69. 7±5. 0)% , respectively. Observed by pathology, apoptosis rate and necrosis number of tumor cells in PLTL group were significantly increased. Conclusion Compared with PTX and PTL, PLTL has an evident thermo-sensitive feature and can increase the anticancer effect of paclitaxel remarkably when combined with local hyperthermia.
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Objective To investigate the effects of periplocin from Cortex Periplocae (CPP) on apoptosis of human lung cancer A549 cells and expression of survivin, and demonstrate its anti-tumor effect and the possible mechanism. Methods Inhibitory effect of CPP at different concentrations (1. 25, 2. 50, 5. 00, 10. 00, 20. 00 ng·mL-1 ) and for different time length (24, 48, 72 h) on A549 cell proliferation was tested by MTT method. Apoptosis rate of A549 cells treated with CPP at different concentrations (2. 50, 5. 00, 10. 00 ng·mL-1 ) were measured using flow cytometry (FCM) for 6, 12, 24, 48, 72 h, respectively. The morphological and ultrastructural changes of the apoptosis cells were observed by acridine orange/ ethidium bromide (AO/ EB) staining and transmission electron microscopy (TEM). The effects of CPP on mRNA and protein expression of apoptosis associated gene survivin were assessed by RT-PCR and Western blotting. Results CPP could significantly inhibit the growth of A549, and the inhibition rate reached (93. 46±2. 35)% . The results of FCM showed that the apoptosis rate of A549 cells treated with CPP was increased significantly as compared to the control group ( P<0. 05). Meanwhile, typical apoptotic peaks were detected. The characteristic morphological changes of apoptosis were observed in A549 exposed to CPP, including cell shrinkage, the nuclei became yellow-red by AO/ EB staining, and typical ultrastructural changes, including nuclear chromatin condensation along the nuclear membrane, vacuolar degeneration of cytoplasm observed by TEM. The result of RT-PCR indicated that survivin mRNA expression decreased obviously in A549 cells exposed to CPP. The protein expression of survivin in A549 cells treated with 10. 0 ng·mL-1 CPP(0. 251±0. 012)was weaker than that in control group(0. 928±0. 016). Conclusion CPP can induce apoptosis in human lung cancer cell lines A549, and the probable mechanism is related to the down-regulation of survivin mRNA and protein.
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Background and purpose:Conventional cytology is valuable in diagnosing the cancer cells in lymph nodes of patients with lung cancer. However , the diagnostic value of detecting lymph node and paracancer micrometastasis was limited. Our study was to investigate the mRNA expression level of lung specif ic X protein(LUNX) and cytokeratin 19(CK19) and its signifi cance in the carcinogenesis,metastasis and prognosis of NSCLC. Methods: Quantitative analysis with reverse transcriptase polymerase chain reaction(Real-Time RT-PCR) was used to detect the mRNA expression level of LUNX and CK19 in 20 tumor tissues and 42 regional lymph nodes from 20 patients with NSCLC, and 6 lymph nodes from 9 patients with pulmonary benign diseases as control. Meanwhile, all lymph nodes were also examined by conventional pathological method. Results:①the mRNA level of Lunxin in cancer Tissue was signifi cantly higher than that in the control group, but there was no association with Lymphatic Metastasis,Tumor Size and TNM grade.②the mRNA level of Lunx in the cancer Tissues was signif icantly higher than that in the control group, and was associated with Lymphatic Metastasis,Tumor Size and TNM grade.③the mRNA of CK19 in lymph nodes was almost the same as control, and not associated with tumor size,lymphatic metastasis and TNM grade.④the mRNA of LUNX in lymph nodes was almost the same as control, which has no acossiation with lymphatic metastasis,tumor size and TNM grade.⑤ mRNA of CK19 and LUNX was unrelated to age,sex and histological type .⑥there was signifi cant difference between using Real-Time RT-PCR methods and the routine pathological methods to detect lymph node metastasis in lung cancer. Conclusion:This result suggested that the detection of LUNX message RNA and CK19message RNA might be helpful to diagnose NSCLC micrometastasis in lymph nodes. LUNX was superior to CK19 both in sensitivity and specifi city. The establishment of this method may increase the positive rate of detecting metastatic regional lymph nodes in non small cell lung cancer.
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One hundred thirty-four lung cancer cases who were histologically proven in life and who had chest x-rays at time of initial diagnosis were entered into this retrospective study covering the period from January 1, 1979 to April 30, 1985The major histologic subtype of lung cancer in this study were similar to those cited by foreign literatures, namely epidermoid cell cancer (37). Adenocarcinoma (25), small cell cancer (20) and large cell cancer (5). By frequency and odds ratio, squamous cell and adenocarcinoma histologies presented with a peripheral radiographic location two times more than with a central location. On the other hand, small cell cancer histology was three times more associated with central radiogaphic presentation. Large cell cancer histology showed to be either centrally or peripherally located without preference. (author)