Psychological Dimensions of Palliative Care Consultation: Approaches to Seriously Ill Patients at the End of Life.

Mental health clinicians often hear seriously ill patients ask the unanswerable: Why did this happen? What is the meaning of my suffering? In the inpatient setting, general medical ward, or oncology unit, patients are confronted with their mortality in new, urgent ways. Palliative medicine, or the specialized, comprehensive care of patients facing a life-limiting illness, occupies a unique and liminal space. Although often practiced by clinicians with non-mental health training backgrounds, there exists ample psychological content to be explored in the palliative care encounter. In this article, we present the case of a husband and international businessperson who experienced terminal complications from an advanced stage lung cancer. His illness was not responsive to multiple cancer-directed treatments, and he developed respiratory failure requiring high levels of supplemental oxygen support, from which he was unable to wean. Palliative care consultation was sought with the multiple objectives of ameliorating his severe death anxiety and persistent dyspnea as well as assisting in the clarification of his end-of-life wishes. Our goal with this case presentation and related discussion is to introduce the psychological aspects of palliative medicine to psychiatrists and psychotherapists.

Cisplatin resistance of NSCLC cells involves upregulation of visfatin through activation of its transcription and stabilization of mRNA.

Non-small cell lung cancer (NSCLC) is one of the prevalent and deadly cancers worldwide. Cisplatin (CDDP) has been used as a standard adjuvant therapy for advanced NSCLC patients, while chemoresistance is one of the most challenging problems to limit its clinical application. Our data showed that the expression of visfatin was significantly increased in CDDP resistant NSCLC cells as compared with that in their parental cells, while knockdown of visfatin or its neutralization antibody can restore the CDDP sensitivity of resistant NSCLC cells. The upregulation of visfatin in CDDP resistant NSCLC cells was due to the increased mRNA stability and promoter activity. Further, we found that signal transducer and activator of transcription 3 (STAT3), which was increased in chemoresistant cells, can increase the transcription of visfatin. While tristetraprolin (TTP), which can decease mRNA stability of visfatin, was decreased in chemoresistant cells. Inhibition of STAT3 or over expression of TTP can restore CDDP sensitivity of resistant NSCLC cells. Collectively, our data showed that STAT3 and TTP-regulated expression of visfatin was involved in CDDP resistance of NSCLC cells. It indicated that targeted inhibition of visfatin should be a potential approach to overcome CDDP resistance of NSCLC treatment.

Prognostic nutritional index as a prognostic factor in lung cancer patients receiving chemotherapy: a systematic review and meta-analysis.

OBJECTIVE: Lung cancer is one of the leading causes of morbidity and mortality in the world. In the past decade, numerous studies focus on the prognostic nutritional index (i.e., a measure of serum albumin and lymphocyte in peripheral circulation) as a possible biomarker to predict the survival outcomes in cancer patients undergoing chemotherapy. Prognostic nutritional index can reliably predict the survivability outcomes by effectively quantifying the nutritional and immunological status of cancer patients. To date, only one review has attempted to evaluate the impact of the prognostic nutritional index on the survival outcomes in lung cancer patients with certain limitations. The goal of the present systematic review and meta-analysis is to bridge the gap in the literature and evaluate the capacity of the prognostic nutritional index for predicting the survivability outcomes in lung cancer patients undergoing chemotherapy. The aim of the study is to evaluate the impact of prognostic nutritional index scoring on survival outcomes in lung cancer patients undergoing chemotherapy. MATERIALS AND METHODS:  A systematic academic literature search was performed based on the PRISMA guidelines across Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE databases. A random-effect meta-analysis was performed to evaluate the impact of prognostic nutritional index scoring (i.e., high/low) on survival outcomes (i.e., progression-free survival, overall survival) in lung cancer patients undergoing chemotherapy. RESULTS:  From 963 studies, 16 eligible studies with 4250 lung cancer patients (62.32 ± 5.08 years) undergoing chemotherapy were included. Our meta-analysis revealed worse mortality outcomes in terms of progression-free survival (HR: 1.31) and overall survival (1.21) for the group with a low prognostic nutritional index score as compared to the group with a high prognostic nutritional index score in lung cancer patients undergoing chemotherapy. Subsequent subgroup analyses further demonstrated markedly worse outcomes for progression-free survival (1.32) and overall survival (1.52) in non-small lung cancer patients with lower prognostic nutritional index scores. CONCLUSIONS:  We provide preliminary evidence suggesting that lower prognostic nutrition index scores are associated with worse survivability outcomes (progression-free survival and overall survival) in lung cancer patients undergoing chemotherapy. We also show that lower prognostic nutrition index scores correlate with even worse survival outcomes in patients with non-small lung cancer histological subtype of lung cancer. These findings should help clinicians to stratify the risks associated with the chemotherapeutic management of lung cancer patients.

Nonpharmacological interventions for cancer-related fatigue in lung cancer patients: A protocol for an evidence map of overview of a network meta-analysis of existing trials.

BACKGROUND: Lung cancer is one of the most common cancers, the symptoms and treatment of which can cause negative emotions like anxiety, depression, and cancer-related fatigue (CRF). Nonpharmacological interventions, serving as alternative therapies, can greatly alleviate CRF in lung cancer patients. Previous meta-analyses have reported nonpharmacological interventions of CRF in lung cancer patients, but the results may be conflicting, and the reporting and methodological qualities remain unknown. Moreover, there is limited evidence to identify efficient and safe non-pharmacological interventions of CRF in lung cancer patients. This study aims to assess the therapeutic efficacy of nonpharmacological interventions of CRF in lung cancer patients through a network meta-analysis. METHODS: Relevant literatures reporting non-pharmacological interventions of CRF in lung cancer patients published before June 2021 will be searched in online databases, including Wanfang, VP Information Chinese Journal Service Platform, China National Knowledge Infrastructure, Chinese BioMedicine Literature Database, PubMed, Embase, Cochrane, and Web of science. Two reviewers will be independently responsible for study selection, quality appraisal, and data extraction. Data analysis will be performed using the STATA14.0 and GEMTC 0.14.3 software. RESULTS: This meta-analysis will provide additional and stronger evidences for nonpharmacological interventions of CRF in lung cancer patients. Our findings will be conductive to make therapeutic decisions by clinicians. CONCLUSION: This study will provide a reliable evidence-based basis for non-pharmacological interventions of CRF in lung cancer patients. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/QRY42.

Rh2-enriched Korean ginseng (Ginseng Rh2+) inhibits tumor growth and development of metastasis of non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: While there are multiple studies on the anti-tumoral effects of Panax ginseng as active ingredients (one or more ginsenosides derived from the extract) or as a whole plant extract, there is a lack of studies to assess the effects Panax ginseng's of active ingredients combined with the whole plant extract. Our aim was to study the effect of whole ginseng, enriched in the anti-tumoral Rh2 component and other ginsenosides (Ginseng Rh2+), on the metastatic capacity of non-small cell lung cancer (NSCLC). METHODS: We evaluated the effects of Ginseng Rh2+ on survival, migration and motility, induction of apoptosis, and expression of its apoptosis-related proteins in non-small cell lung cancer (NSCLC) cells in vitro and on primary tumor growth and metastatic capacity in a syngeneic mouse lung cancer model in vivo. The effects of Ginseng Rh2+ on NSCLC cells were studied in vitro using: a colorimetric tetrazolium salt (XTT) assay, annexin V-FITC/PI, western blotting, wound healing motility assay, Transwell migration and cell adhesion assays. In vivo, mice were inoculated with Lewis mouse lung carcinoma cells subcutaneously to evaluate local tumor growth, or intravenously to evaluate the effects of Ginseng Rh2+ on development of experimental metastases. Mice were treated by intraperitoneal administration of Ginseng Rh2+ (0.005-0.5 g kg-1) on days 6, 10, and 14 after tumor injection. RESULTS: We found that Ginseng Rh2+ increased the apoptosis of NSCLC cells in vitro, demonstrating dose dependent down-regulation of the Bcl-2 anti-apoptotic gene and concurrent up-regulation of the Bax pro-apoptotic gene. Ginseng Rh2+ inhibited the tumor cells' capacity to attach to the ECM-related matrix and reduced cell migration. In vivo, Ginseng Rh2+ inhibited local tumor growth and reduced the development of experimental lung metastases. CONCLUSION: Our study suggests that Ginseng Rh2+ may potentially be used as a therapeutic agent for treatment of NSCLC.

Prognostic impact of the pre-treatment controlling nutritional status score in patients with non-small cell lung cancer: A meta-analysis.

BACKGROUND: The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed this meta-analysis to evaluate the prognostic significance of CONUT score in NSCLC patients. METHODS: A systematic literature review was conducted using PubMed, Embase, and the Cochrane Library databases. The hazard ratio (HR) and 95% confidence interval (CI) were extracted to assess the correlation between the CONUT score and the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), as well as the cancer-specific survival. RESULTS: A total of 11 studies with 3029 patients were included in the analysis. Pooled results indicated that a high CONUT score was positively correlated with poor OS (HR: 1.63, 95%CI: 1.40-1.88, P < .001) and shortened DFS/RFS (HR: 1.65, 95%CI: 1.35-2.01, P < .001), but no significant relationship with the cancer-specific survival (HR: 1.28, 95%CI: 0.60-2.73, P = .517) was identified. The negative effect of high CONUT score on the OS and DFS/RFS was detected in every subgroup with varying treatment methods, cancer stage, CONUT cut-off values, sample size, and analysis methods of HR. Additionally, preoperative high CONUT score was an independent predictor of postoperative complications (odds ratio: 1.58, 95%CI: 1.21-2.06, P = .001) in NSCLC. Last but not least, high CONUT score was not significantly correlated with the patients' sex, smoking status, cancer stage, lymphatic invasion, vascular invasion, pleural invasion, and pathological cancer type. CONCLUSION: These results demonstrate that high CONUT score is positively related to poor prognoses. The CONUT score may therefore be considered as an effective prognostic marker in NSCLC patients.

[Comparison of Short-term Results of Preoperative Planning Combined with 
Fluorescence Video-assisted Thoracoscopic Precision Segmentectomy and Traditional Thoracoscopic Segmentectomy in the Treatment of Early Lung Adenocarcinoma].

BACKGROUND: The mortality of lung cancer ranks first among all malignant tumors, but there are few studies on the effect of different segmentectomy on lung function in patients with early lung adenocarcinoma. The purpose of this study was to evaluate the degree of lung function preservation and short-term results of preoperative planning combined with fluorescence thoracoscopic precision segmentectomy and traditional segmentectomy in patients with early lung adenocarcinoma. METHODS: From January 1, 2020 to October 31, 2020, 60 patients underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of the First Affiliated Hospital of University of Science and Technology of China: 30 patients in precision segmentectomy group and 30 patients in traditional segmentectomy group. The clinicopathological features, perioperative data and postoperative pulmonary function of the two groups were compared. RESULTS: The operation time of the precision group was shorter than that of the traditional group, and the difference was statistically significant (P<0.05). The preoperative pulmonary function accuracy group and the traditional group in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and carbon monoxide diffusing capacity (DLCO) were (3.65±0.63) L vs (3.54±0.64) L, (2.72±0.50) L vs (2.54±0.48) L and (20.36±3.02) mL/mmHg/min vs (19.16±3.18) mL/mmHg/min, respectively. One month after operation, the FVC, FEV1 and DLCO of pulmonary function accuracy group and traditional group were (3.35±0.63) L vs (2.89±0.57) L, (2.39±0.54) L vs (2.09±0.48) L and (17.43±3.10) mL/mmHg/min vs (15.78±2.865) mL/mmHg/min, respectively. Three months after operation, the FVC and DLCO of pulmonary function accuracy group and traditional group were (3.47±0.63) L vs (3.20±0.56) L and (19.38±3.02) mL/mmHg/min vs (17.79±3.21) mL/mmHg/min, respectively. CONCLUSIONS: Preoperative planning combined with fluorescence thoracoscopic precise segmentectomy provides advantages in intersegmental plane recognition, vascular anatomy and postoperative recovery, which significantly shortens the operation time and makes the treatment more accurate.

Long-term progression-free survival in a patient with advanced non-small-cell lung cancer treated with low-dose gefitinib and traditional herbal medicine: A case report.

RATIONALE: Gefitinib is a first-line palliative chemotherapy drug used to treat advanced non-small-cell lung cancer (NSCLC) in patients who have an epidermal growth factor receptor (EGFR) mutation. However, approximately two-thirds of NSCLC patients with EGFR-tyrosine kinase inhibitor experience dermatological toxicity. Cutaneous toxicity is usually not life threatening but can necessitate modification or discontinuation of medication in severe cases. In this case, despite a reduction in the dose of gefitinib due to side effects, combined treatment with modified Bojungikki-tang (BJKIT) increased progression-free survival (PFS) in an advanced NSCLC patient. PATIENT CONCERNS: An 83-year-old Asian woman presented with chief complaints of chronic cough, dyspnea, weight loss, and anorexia. DIAGNOSES: The patient was diagnosed with stage IV NSCLC (T2aN3M1), adenocarcinoma with metastasis to the lymph node, brain, and bone based on image scan and biopsy. An EGFR deletion was detected in exon 19. INTERVENTIONS: The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT). However, after 1 year of combination therapy, gefitinib was tapered down to once per week while modified BJIKT was maintained. OUTCOMES: A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months. LESSONS: Despite the reduction in gefitinib dose due to side effects, the combined treatment of gefitinib and the modified BJIKT has maintained a PFS of over 78 months, indicating that modified BJIKT enhanced the anti-cancer effect of gefitinib in a patient with advanced NSCLC harboring the EFGR mutation, and may have delayed acquired resistance, the main limitation on the efficacy of gefitinib. Further investigations including clinical trials are needed to confirm these effects.

Effect of extract from Yiyuan Yiliu Tang on human lung adenocarcinoma and human hepatoma cell lines.

OBJECTIVE: To investigate the efficacy of the extract from Yiyuan Yiliu Tang (, YYYLT) on human lung adenocarcinoma cells A549 and human hepatoma cells Bel7402. METHODS: The cancer cell lines were treated with various concentrations (0, 100, 200, 300, and 400 µg/mL) of the crude water extract of YYYLT and then cell viability, toxicity, cytokine secretion, and cell cycle/apoptosis were determined by MTT assay, LDH assay, and flow cytometry, respectively. RESULTS: The extract from YYYLT significantly suppressed the proliferation of the cancer cell lines and the release of interleukin-2 and tumor necrosis factor-α in a dose-dependent manner. The extract also promoted apoptosis, caused cell cycle arrest at G0/G1 phase, and increased the expression of caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X proteins. CONCLUSION: The extract from YYYLT might be a potential treatment for human lung and liver cancers.

Efficacy of ginseng and its ingredients as adjuvants to chemotherapy in non-small cell lung cancer.

Chemotherapy is applied to treat non-small cell lung cancer (NSCLC), but often limited due to its unstable therapeutic effects and adverse reactions (ADRs). Ginseng and its main ingredients (ginsenosides and polysaccharides) have been clinically used as adjuvants to chemotherapy. However, their efficacies were based on individual trials with relatively small sample sizes, and it is difficult to draw a valid conclusion. In this study, eligible randomized controlled trials (RCTs) were searched in six international and Chinese databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang). The outcomes of the objective response rate (ORR), disease control rate (DCR), ADRs, quality of life (QOL), survival rates and immunity were extracted using standard data extraction forms. The efficacies of ginseng and its ingredients as adjuvants to chemotherapy in NSCLC were investigated and compared by meta-analysis and subgroup meta-analysis, respectively. A total of 28 RCTs including 2503 subjects were enrolled, and most of the eligible studies were of low-to-moderate quality. For the evaluation of ginseng and its ingredients as adjuvants to chemotherapy, the risk ratio (RR) or standardized mean difference (SMD) and 95% confidence intervals (CI) of the ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, nausea and vomiting, diarrhea, CD4+/CD8+ and one- and two-year survival rates, and QOL were 1.35 (1.21,1.50), 1.20 (1.14,1.28), 0.59 (0.50, 0.70), 0.53 (0.37, 0.76), 0.30 (0.17, 0.53), 0.67 (0.52, 0.87), 0.67 (0.53, 0.86), 0.42 (0.19, 0.96), 1.39 (0.63, 2.16), 1.35 (1.13, 1.60), 3.21 (1.51, 6.81) and 1.31 (1.22, 1.41) with significant differences. Subgroup analysis showed that ginseng enhanced nausea and vomiting and QOL, ginsenosides increased ORR, DCR, QOL, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, diarrhea, CD4+/CD8+, and one- and two-year survival rates, while polysaccharides improved ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity and nausea and vomiting during chemotherapy. In conclusion, ginseng and its ingredients facilitated the therapeutic effects of chemotherapy on NSCLC patients. Ginseng had beneficial effects on alleviating ADRs and enhancing QOL, ginsenosides demonstrated beneficial effects on enhancing therapeutic effects, reducing ADRs, improving immunity, prolonging survival rates and promoting QOL, while polysaccharides showed beneficial effects on promoting therapeutic effects and reducing ADRs.

Feasibility of a multimodal intervention on malnutrition in patients with lung cancer during primary anti-neoplastic treatment.

BACKGROUND: Wasting of body mass and skeletal muscle frequently develops in patients with cancer and is associated with impaired functional ability and poor clinical outcome and quality of life. This study aimed to evaluate the feasibility and explore the effect of a multimodal intervention targeting nutritional status in patients with non-small cell lung cancer receiving primary anti-neoplastic treatment. Additionally, predictive and prognostic factors of gaining skeletal muscle were explored. METHODS: This was a single-centre multimodal intervention trial using a historical control group. The multimodal intervention involved fish oil intake (2 g of eicosapentaenoic acid or docosahexaenoic acid daily), regular dietary counselling and unsupervised physical exercise twice weekly during the first three cycles of primary anti-neoplastic treatment. Feasibility was assessed through recruitment rate, completion rate and compliance rate with the intervention. Differences in skeletal muscle, body weight, and physical function between the intervention and historical control groups were analysed. Factors contributing to increased skeletal muscle were explored using univariate and multivariate ordinal logistic regression analyses. RESULTS: The recruitment and completion rates were 0.48 (n = 59/123) and 0.80 (n = 46/59), respectively. The overall compliance rate with all five individual interventions was 0.60 (n = 28/47). The individual compliance rates were 0.81 (n = 38/47) with fish oil intake, 0.94 (n = 44/47) with energy intake, 0.98 (n = 46/47) with protein intake, 0.51 (n = 24/47) with resistance exercise and 0.57 (n = 27/47) with aerobic exercise. No mean differences in skeletal muscle, body weight, or physical function were found between the intervention and control groups. However, a larger proportion of patients in the intervention group gained skeletal muscle (p < 0.02). The identified contributing factors of muscle gain were weight gain (OR, 1.3; p = 0.01), adherence to treatment plan (OR, 4.6; p = 0.02), stable/partial response (OR, 3.3; p = 0.04) and compliance to the intervention (OR, 7.4; p = 0.01). Age, sex, tumour stage, performance status, treatment type and baseline cachexia did not predict muscle gain. CONCLUSION: This three-dimensional intervention in patients with lung cancer undergoing primary anti-neoplastic treatment was feasible and increased the proportion of patients gaining skeletal muscle. Dietary counselling and fish oil use were useful strategies. The motivation for conducting unsupervised physical intervention was low. Clinical trials.gov identifier: NCT04161794.

Herbal formula Renshenwuweizi decoction induces p53-mediated cell cycle arrest and apoptosis in A549 cells.

OBJECTIVE: To investigate the effect of Renshenwuweizi decoction (RSWWZ decoction) on the growth of non-small cell lung cancer cells in vitro. METHODS: A549 non-small cell lung cancer cells were divided into two groups: control and RSWWZ decoction treatment groups. Cell Counting Kit-8 was used to measure the inhibitory effect of RSWWZ decoction on the growth of A549 cells. 4', 6-diamidino-2-phenylindole staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining were used to investigate apoptosis in A549 cells following RSWWZ decoction treatment, and the mitochondrial membrane potential of treated cells was detected with Rhodamine 123. Cell cycle progression was analyzed by flow cytometry. The mRNA levels of p53, Bax, B-cell lymphoma-2 (Bcl-2) and p21 were measured by quantitative real-time reverse transcription polymerase chain reaction. The protein expressions of p53, Bax, Bcl-2, p21, cyclin-dependent kinases 2 (CDK2), and cyclin A were detected by Western blot. RESULTS: RSWWZ decoction reduced the viability of A549 cells in a dose-dependent manner by inducing apoptosis and decreased mitochondrial membrane potential. RSWWZ decoction increased p53 and Bax expression and decreased Bcl-2 expression in a dose-dependent manner. RSWWZ decoction also induced an S-phase cell cycle arrest by increasing p21 and decreasing cyclin A and CDK2 expression. CONCLUSION: In vitro experiments revealed that the Renshenwuweizi decoction-induced decrease in A549 cell proliferation was achieved by inducing apoptosis and S-phase cell cycle arrest via the p53 pathway. These findings provide the experimental basis for Renshenwuweizi decoction treatment of lung cancer.

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.

PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Hyperthermia, positive feedback loop with IL-6 and risk of NSCLC progression: a tangle to unravel?

Fever may represent a risk factor for NSCLC by increasing IL-6 expression. In this light, an accurate and rapid control of fever among lung cancer patients should be carefully added to the treatment plan. On this regard, concerns increase when doubts arise regarding the applicability of hyperthermia on NSCLC given the potential interaction of IL-6 with NSCLC. Thus, I suggest that randomized, controlled double-arm clinical studies are warranted for an evidence-based evaluation of feasibility of the hyperthermia application in the management of NSCLC.

Assessment of gait parameters and physical function in patients with advanced cancer participating in a 12-week exercise and nutrition programme: A controlled clinical trial.

OBJECTIVE: Gait is a sensitive marker for functional declines commonly seen in patients treated for advanced cancer. We tested the effect of a combined exercise and nutrition programme on gait parameters of advanced-stage cancer patients using a novel wearable gait analysis system. METHODS: Eighty patients were allocated to a control group with nutritional support or to an intervention group additionally receiving whole-body electromyostimulation (WB-EMS) training (2×/week). At baseline and after 12 weeks, physical function was assessed by a biosensor-based gait analysis during a six-minute walk test, a 30-s sit-to-stand test, a hand grip strength test, the Karnofsky Index and EORTC QLQ-C30 questionnaire. Body composition was measured by bioelectrical impedance analysis and inflammation by blood analysis. RESULTS: Final analysis included 41 patients (56.1% male; 60.0 ± 13.0 years). After 12 weeks, the WB-EMS group showed higher stride length, gait velocity (p < .05), six-minute walking distance (p < .01), bodyweight and skeletal muscle mass, and emotional functioning (p < .05) compared with controls. Correlations between changes in gait and in body composition, physical function and inflammation were detected. CONCLUSION: Whole-body electromyostimulation combined with nutrition may help to improve gait and functional status of cancer patients. Sensor-based mobile gait analysis objectively reflects patients' physical status and could support treatment decisions.

Preoperative respiratory muscle endurance training improves ventilatory capacity and prevents pulmonary postoperative complications after lung surgery.

BACKGROUND: Resection surgery is the main treatment for non-small cell lung cancer (NSCLC). Postoperative complications and mortality are mostly linked to respiratory failure consecutive to respiratory muscle overload. AIM: We aimed to evaluate the effect of preoperative respiratory muscle endurance training (RMET) on respiratory muscle capacity and postoperative complications in patients undergoing NSCLC resection. DESIGN: Randomized controlled trial. SETTING: French university hospital. POPULATION: Patients eligible for NSCLC resection. METHODS: The training group (T group) performed a 3-week preoperative RMET added to usual chest physical therapy while the control group (C group) had only the latter. The primary outcome was the change in respiratory muscle endurance. Secondary outcomes were postoperative complications and mortality. Assessments were performed similarly at baseline and after the intervention. We conducted multivariable analyses with analysis of covariance (ANCOVA) taking into account baseline values for isocapnic hyperpnoea endurance test, exercise capacity and pulmonary function tests. The number of pulmonary postoperative complication was analyzed by Fisher-exact test. RESULTS: We included 26 patients with NSCLC (14 in the T group and 12 in the C group). Respiratory muscle endurance significantly increased in the T group after the RMET compared with C group (+229±199 vs. -5±371 sec, P=0.001). This increase was associated with a significantly lower number of pulmonary postoperative complications (2 vs. 10, P=0.037). CONCLUSIONS: Preoperative RMET improved respiratory muscle endurance and decreased pulmonary postoperative complications after surgery for NSCLC. These positive results obtained after RMET may help improve the perioperative course for such patients. These results should be confirmed in larger randomized controlled trials, including higher number of patients especially with altered respiratory muscle function. CLINICAL REHABILITATION IMPACT: Low-cost and easy to perform, RMET training could serve as complementary tool to usual chest physical therapy, before lung resection surgery.

Bee Venom Suppresses EGF-Induced Epithelial-Mesenchymal Transition and Tumor Invasion in Lung Cancer Cells.

Bee venom of Apis mellifera is a traditional medicine in Asia. It has been used with promoting results for the treatment of pain, rheumatoid, and cancer disease. The purpose of this study was to investigate the effects of bee venom on epidermal growth factor (EGF)-induced epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) and determine possible signaling pathway affected in EGF-induced EMT in A549 cells. Bee venom inhibited EGF-induced F-actin reorganization and cell invasion, and suppressed EGF-induced EMT, processes associated with tumor metastasis in NSCLC. Bee venom enhanced the upregulation of E-cadherin and the downregulation of vimentin and inhibited EGF-induced ERK, JNK, FAK, and mTOR phosphorylation in A549 cells. However, the inhibition of JNK phosphorylation by bee venom was not related to the inhibitory effects of EMT. Furthermore, we found that bee venom suppressed the EMT-related transcription factors ZEB2 and Slug by blocking EGF-induced ERK, FAK and mTOR phosphorylation. Bee venom inhibits EGF-induced EMT by blocking the phosphorylation of ERK, FAK, and mTOR, resulting in the suppression of ZEB2 and Slug. These data suggest bee venom as a potential antimetastatic agent for NSCLC.

How Ginsenosides Trigger Apoptosis in Human Lung Adenocarcinoma Cells.

Panax ginseng is a natural medicine that has been used globally for a long time. Moreover, several studies have reported the effective activity of ginseng in treating malignancies. Various agents containing ginseng were widely used as an antitumor treatment nowadays. Lung cancer is the most common fatal cancer in China, and lung adenocarcinoma is the most common histological type of non-small cell lung cancer (NSCLC). What's worse, many patients may have a failed response to conventional therapy including chemotherapy, radiotherapy, or molecule-targeted therapy due to drug resistance. Apoptosis is a highly ordered cellular suicidal process that plays an essential role in maintaining normal homeostasis. The pharmacological mechanism of many antineoplastic drugs involves triggering of apoptotic process. In several recent studies, ginsenosides are regarded as major active components of ginseng that have the potential to control lung cancer. Most of these results have proved that ginsenosides induce apoptosis in lung cancer cells through many different signaling pathways such as PI3K/Akt, NF-κB, EGFR, and so on. This study is aimed at reviewing the signaling pathways that underlie ginsenosides-triggered apoptotic process and encourage further studies to target promising agents against lung cancer treatment.

Inhibitory effects of polyphyllins I and VII on human cisplatin-resistant NSCLC via p53 upregulation and CIP2A/AKT/mTOR signaling axis inhibition.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer (NSCLC). CIP2A plays an 'oncogenic nexus' to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and mTORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/mTOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I (PPI) and polyphyllin VII (PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin (DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/mTOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of mTOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.