Pulmonary Rehabilitation Exercises Effectively Improve Chronic Cough After Surgery for Non-small Cell Lung Cancer.

INTRODUCTION: Cough is a major complication after lung cancer surgery, potentially impacting lung function and quality of life. However, effective treatments for managing long-term persistent postoperative cough remain elusive. In this study, we investigated the potential of a pulmonary rehabilitation training program to effectively address this issue. METHODS: Between January 2019 and December 2022, a retrospective review was conducted on patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and lymph node dissection via video-assisted thoracoscopic surgery (VATS) at Daping hospital. Based on their postoperative rehabilitation methods, the patients were categorized into 2 groups: the traditional rehabilitation group and the pulmonary rehabilitation group. All patients underwent assessment using the Leicester cough questionnaire (LCQ) on the third postoperative day. Additionally, at the 6-month follow-up, patients' LCQ scores and lung function were re-evaluated to assess the long-term effects of the pulmonary rehabilitation training programs. RESULTS: Among the 276 patients meeting the inclusion criteria, 195 (70.7%) were in the traditional rehabilitation group, while 81 (29.3%) participated in the pulmonary rehabilitation group. The pulmonary rehabilitation group showed a significantly lower incidence of cough on the third postoperative day (16.0% vs 29.7%, P = .018) and higher LCQ scores in the somatic dimension (5.09 ± .81 vs 4.15 ± 1.22, P = .007) as well as in the total score (16.44 ± 2.86 vs 15.11 ± 2.51, P = .018, whereas there were no significant differences in psychiatric and sociological dimensions. At the 6-month follow-up, the pulmonary rehabilitation group continued to have a lower cough incidence (3.7% vs 12.8%, P = .022) and higher LCQ scores across all dimensions: somatic (6.19 ± .11 vs 5.75 ± 1.20, P = .035), mental (6.37 ± 1.19 vs 5.85 ± 1.22, P = .002), sociological (6.76 ± 1.22 vs 5.62 ± 1.08, P < .001), and total (18.22 ± 2.37 vs 16.21 ± 2.53, P < .001). Additionally, lung function parameters including FVC, FVC%, FEV1, FEV1%, MVV, MVV%, DLCO SB, and DLCO% were all significantly higher in the pulmonary rehabilitation group compared to the traditional group. CONCLUSION: Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Assessment of Measurement Uncertainty for S-Parameter Measurement Based on Covariance Matrix.

S-parameters are widely used to detail the scattering parameters of radio frequency (RF) components and microwave circuit modules. The vector network analyzer (VNA) is the most commonly used device for measuring S-parameters. Given the multiple frequency points, complex values, and intricate uncertainty propagation involved, accurately assessing the uncertainty of S-parameter measurements is difficult. In this study, we proposed a new method for assessing S-parameter uncertainty based on the covariance matrices, tracing back to the nominal uncertainty of calibration standards. First, we analyzed the relevant theory of uncertainty assessment using covariance matrices and subsequently deduced the mechanism of Type B uncertainty propagating from calibration standards to error model coefficients and S-parameter measurements to evaluate Type B measurement uncertainty. In this study, a novel measurement system was constructed for measuring grounded coplanar waveguides by using a VNA and calibration standards with 8- and 12-error models. Initially, the model assessed the Type B uncertainty of measuring four S-parameters of a grounded coplanar waveguide. Next, the VNA calibrated with the 12-error model was used to conduct multiple repeated measurements to assess the Type A uncertainty of the grounded coplanar waveguide. Finally, the composite uncertainty was constructed, which demonstrated that the proposed method can be used for assessing the uncertainty of S-parameters.

Method to Change the Through-Hole Structure to Broaden Grounded Coplanar Waveguide Bandwidth.

A grounded coplanar waveguide (GCPW), as a millimeter wave special transmission line, can be used to calibrate broadband oscilloscope probes. A method to change the through-hole structure to widen the GCPW is investigated in this paper. The effect of the through-hole array on the band-width of the GCPW is investigated and verified using COMSOL Multiphysics simulation software. Finally, the S-parameters of the fabricated GCPWs are measured by a vector network analyzer, and the results show that they have an insertion loss > -3 dB and return loss < -10 dB in the frequency range of DC to 60 GHz, which satisfies the design requirements.

Primary Mediastinal Nonseminomas: A Population-Based Surveillance, Epidemiology, and End Results Analysis.

BACKGROUND: This study aimed to determine the disease characteristics and prognosis of patients with primary mediastinal nonseminomas (PMNS) in a Surveillance, Epidemiology, and End Results (SEER) analysis. MATERIALS AND METHODS: Demographic, treatment, and survival outcome data of cases with PMNS from 1975 to 2016 were retrieved. Cases with unknown variables mentioned in the analysis were excluded. Relative statistical methods were applied to analyze clinical characteristics and prognosis. RESULTS: A total of 587 PMNS patients met the selection criteria, 526 of whom were men. The mean age of patients was 28 (1-85) y. A total of 511 PMNS patients had validated subtypes, including 172 mixed germ cell tumors, 117 yolk sac tumors, 111 malignant teratomas, 70 choriocarcinomas, and 41 embryonal carcinomas. Patients with yolk sac tumors had the highest 3-y cancer-specific survival (CSS) rate (66.9%), while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Surgery + chemotherapy (46.2%) was the most common and effective treatment for each subtype of PMNS. Multivariate Cox proportional hazards analysis identified embryonal carcinoma, malignant teratoma, choriocarcinoma, tumor size >15 cm, nodal metastasis, and distant stage as risk factors. In contrast, surgery-based care and younger age were protective factors. Propensity score matching analysis revealed significant improvement in the 5-y CSS rate from 35.8% to 60.3% with surgery (P < 0.001). However, radiotherapy (P = 0.436) and chemotherapy (P = 0.978) showed no survival benefits. CONCLUSIONS: 10 percent of the PMNS patients were female. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery was demonstrated to be the only way to prolong survival time. Chemotherapy and radiotherapy had minimal effects on prognosis.

Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. DATA SOURCES: PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. STUDY SELECTION: Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. DATA EXTRACTION: Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. CONCLUSIONS: BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.

Effect of mesotherapy with nanochip in the treatment of facial rejuvenation.

Objective: To observe the clinical effect of mesotherapy with nanochip for facial rejuvenation.Methods: 24 volunteers with aging skin were treated with a polycomponent formulation - NCTF® BOOST 135 HA for 5 times (once weekly for 3 times and successively biweekly for 2 times). Photographs were taken by VISIA at baseline, and after 1, 4, 10 weeks, while global scores for photoaging (GSP), improvement scores, volunteers' satisfaction, parameters describing the properties of the skin, and adverse effects were assessed during each follow-up period.Results: Total 20 volunteers completed the treatment. Evaluation of the whole face showed that GSP, skin texture (ophthalmic wrinkles, dermal thickness, and intensity of collagen fibers of skin), and skin brightness (Lab value) significantly improved at 4 weeks compared to baseline, while the difference between 4 and 10 weeks was not statistically significant. No evident improvement was observed in pigmented spots, telangiectasia, skin tightening, trans-epidermal water loss (TEWL), and skin hydration. Slight erythema, pain was the most common side effect.Conclusion: Mesotherapy with nanochip can improve skin texture and brightness, but the effect is not permanent. It is recommended that the treatment be used as a complementary method for patients with facial rejuvenation needs.

Survival Benefit of Left Lower Paratracheal (4L) Lymph Node Dissection for Patients with Left-Sided Non-small Cell Lung Cancer: Once Neglected But of Great Importance.

OBJECTIVE: The aim of this study was to compare survival outcomes between non-small cell lung cancer (NSCLC) patients with or without 4L node dissection (4LND) and to evaluate the potential patient population who will particularly benefit from 4LND. METHODS: Between January 2009 and December 2015, a total of 2063 patients with primary left-sided NSCLC in the Western China Lung Cancer Database were initially reviewed. After exclusion, 1064 patients were enrolled in this study. A total of 460 patients with 4LND (4LND+ group) were matched with 460 patients without 4LND (4LND- group) using propensity-matched analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The metastasis rate of station 4L was 14.6%. Patients with 4LND showed higher DFS (5-year DFS 52.6% vs. 46.7%; hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.03-1.50; p = 0.022) and OS (5-year OS 65.8% vs. 56.3%; HR 1.36, 95% CI 1.10-1.69; p = 0.006) than patients without 4LND. In the multivariate analysis, patients without 4LND (HR 1.33, 95% CI 1.07-1.66; p = 0.011), tumor size > 3 cm, lymph node metastasis, and pathologic stage higher than stage I were independent prognostic factors for poor OS. Subgroup analysis according to pathologic TNM stage and N stage showed that stage II, IIIA, and N2 disease indicated better survival outcomes in the 4LND+ group (p = 0.050, p = 0.016, and p = 0.008, respectively). CONCLUSIONS: Performing 4LND may bring survival benefits to patients with left-sided NSCLC. We suggest 4LND as a standard procedure for left-sided NSCLC patients with stage II or advanced stage disease.

Clostridium butyricum regulates visceral hypersensitivity of irritable bowel syndrome by inhibiting colonic mucous low grade inflammation through its action on NLRP6.

Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1ß, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18 and IL-1ß were also increased after the NLRP6 gene was silenced. Pathological score suggested low inflammation of colonic mucous rather than terminal ileum. Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic distension. However, treatment with Clostridium butyricum reversed these results, exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.

[Diagnosis and Surgical Treatment of Lung Ground-glass Opacities:a Review of 663 Cases].

OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

[Long term outcomes of patients with stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery lobectomy or segmentectomy].

OBJECTIVE: To observe the outcome of stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery (SD-VATS) major lung resection. METHODS: Between May 2006 and December 2013, a total of 3 743 patients with lung cancer underwent surgical treatment in Department of Thoracic Surgery, West China Hospital. The clinical date of 783 patients with stage I lung cancer treated by SD-VATS lobectomy/segmentectomy was analyzed retrospectively. There were 388 males and 395 females with a mean age of (59 ± 10) years (range 25 to 86 years). There were 740 cases of lobectomy and 43 cases of segmentectomy. Twenty patients underwent conversion to open thoracotomy. The methods of Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to investigate the long term outcome and prognostic factors. RESULTS: The mean operating time was (145 ± 54) minutes (range 70 to 460 minutes). The median intraoperative blood loss was 50 (70) ml (range 5 to 1 200 ml). The postoperative morbidity and 90-day mortality were 13.3% and 1.0%, respectively. 5.9% patients were lost to follow-up. Finally 730 patients were enrolled into prognostic analysis with a mean follow-up time of (37 ± 18) months (range 5 to 92 months). The 5-year overall survival (OS), disease free survival (DFS), and cancer specific survival (CSS) were 83.8%, 74.4%, and 86.6%, respectively. The 5-year OS of IA and IB were 90.7% and 79.8% respectively. Univariate and multivariate analysis indicated that age ≥ 60 years (OR = 1.786, 95% CI: 1.081 to 2.948, P = 0.023), non-adenocarcinoma (OR = 1.647, 95% CI: 1.204 to 2.253, P = 0.002), and higher T status (OR = 2.709, 95% CI: 1.031 to 7.121, P = 0.043) were independently associated with poor OS; higher T status (OR = 5.118, 95% CI: 2.330 to 11.240, P = 0.000) and higher pathological stage status (OR = 0.369, 95% CI: 0.137 to 0.991, P = 0.048) were independently associated with poor DFS; non-adenocarcinoma (OR = 1.717, 95% CI: 1.224 to 2.409, P = 0.002) and higher T status (OR = 5.029, 95% CI: 1.432 to 17.659, P = 0.012) were independently associated with poor CSS. CONCLUSION: SD-VATS lung cancer resection is a safe and feasible method for the treatment of stage I lung cancer resulting good outcomes.

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.

Heat shock protein 70 (HSP70) is a highly conserved protein functioning as a "molecular chaperone", which is integral to protein folding and maturation. In addition to its high expression within cells upon stressful challenges, HSP70 can be translocated to the cell membrane or released from cells in free form or within extracellular vesicles (EVs). Such trafficking of HSP70 is also present in cancer cells, as HSP70 is overexpressed in various types of patient samples across a range of common malignancies, signifying that extracellular HSP70 (eHSP70) can serve as a tumor biomarker. eHSP70 is involved in a broad range of cancer-related events, including cell proliferation and apoptosis, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), angiogenesis, and immune response. eHSP70 can also induce cancer cell resistance to various treatments, such as chemotherapy, radiotherapy, and anti-programmed death-1 (PD-1) immunotherapy. Though the role of eHSP70 in tumors is contradictory, characterized by both pro-tumor and anti-tumor effects, eHSP70 serves as a promising target in cancer treatment. In this review, we comprehensively summarized the current knowledge about the role of eHSP70 in cancer progression and treatment resistance and discussed the feasibility of eHSP70 as a cancer biomarker and therapeutic target.

Investigating esophageal sarcomatoid carcinoma and its comparison with esophageal squamous cell carcinoma on clinicopathological characteristics, prognosis, and radiomics features: a retrospective study.

Introduction: Esophageal sarcomatoid carcinoma (ESC) is a rare pathological subtype of esophageal carcinomas, wherein its epithelial component typically demonstrates squamous cell carcinoma (SCC). However, the clinicopathological features and prognosis of ESC remain unclear, alongside its unique aspects compared to esophageal SCC (ESCC). Methods: Between January 2008 and December 2018, we retrospectively reviewed 67 ESC patients treated at West China Hospital. Among them, 51 patients with resected ESC were matched with 98 resected ESCC patients over the same period using propensity score matching at 1:2. The survival time and radiomics features of the two groups were compared. Results: A total of 59 patients with resected ESC and eight patients with non-resected ESC were enrolled. Progression-free survival (PFS) and overall survival (OS) were significantly different in patients with different TNM stages (p < 0.001). A multivariate analysis showed that length of tumor was an independent factor for OS in resetable ESC (p = 0.041). Among matched ESC and ESCC patients, OS was significantly longer for patients with ESC than those with ESCC (5-year OS, 61.1% vs. 43.6%; HR 0.59, 95% CI 0.35-0.96; p = 0.032). A Rad-score for discriminating ESC from ESCC containing two CT-derived radiomics features was developed [area under the curve: 0.823 (95% CI 0.732-0.913) in the training cohort and 0.828 (95% CI 0.636-1.000) in the validation cohort, respectively]. Conclusions: ESC has a better prognosis when compared with ESCC. By developing a radiomics prediction model, we provide reliability and convenience for the differential diagnosis of ESC from ESCC.

Polyfluorene Conjugated Polyelectrolytes-Covalently Modified Black Phosphorus Nanosheets for Bioinspired Electronics.

As some of the most promising candidates for constituting bioinspired electronics, polymer memristors with analog-type switching behavior exhibit great potential for synaptic mimicking and neuromorphic computing systems. By using highly soluble conjugated polyelectrolyte poly[9,9-bis(6-(3-methyl-1-imidazolium-yl)hexyl)fluorene]-covalently modified black phosphorus (BP) nanomaterial (BP-PF-NMI+Br-) as the active layer, an electronic device with the BP-PF-NMI+Br- film sandwiched between the aluminum and indium tin oxide electrodes is successfully fabricated. This device exhibits an excellent amount of electricity-dependent memristive performance at a small sweep voltage range of ±1 V. With increasing amount of electricity flowing through the device, the device resistance gradually decreased in a linear pattern. The changes in frequency, amplitude, and duration of voltage pulses do not affect the linear relationship between the amount of electricity passing through the device and the resistance value achieved after each state reached equilibrium at different numbers of the same voltage pulse stimulations. Both the synaptic potentiation/depression and learning/memorizing/forgetting functions of biological systems have been emulated. In contrast to BP-PF-NMI+Br-, the pure PF-NMI+Br--based device shows a write-once-read-many-times effect at the same scanning voltage range, while the BP:PF-NMI+Br- blends exhibit very unstable memristive performances.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Heat Shock Proteins in Non-Small-Cell Lung Cancer-Functional Mechanism.

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, which has the highest cancer-related mortality worldwide. Regardless of the therapeutic effects of chemotherapy or targeted therapy, drug resistance will occur after 1 year. Heat shock proteins (HSPs) are a class of molecular chaperones participated in protein stability and multiple intracellular signaling pathways. It has been widely reported that HSPs family is over expressed in non-small cell lung cancer, and these molecules are also associated with protein stability and multiple intracellular signaling pathways. The effect of chemotherapy drugs or targeted drugs on cancer cells is usually to induce apoptosis. It is necessary to explore the interaction between heat shock protein family and apoptosis pathway in NSCLC. Here we provide a brief review of how HSPs affect the apoptotic pathway in NSCLC.

Immunotherapy for Recurrent Glioma-From Bench to Bedside.

Glioma is the most aggressive malignant tumor of the central nervous system, and most patients suffer from a recurrence. Unfortunately, recurrent glioma often becomes resistant to established chemotherapy and radiotherapy treatments. Immunotherapy, a rapidly developing anti-tumor therapy, has shown a potential value in treating recurrent glioma. Multiple immune strategies have been explored. The most-used ones are immune checkpoint blockade (ICB) antibodies, which are barely effective in monotherapy. However, when combined with other immunotherapy, especially with anti-angiogenesis antibodies, ICB has shown encouraging efficacy and enhanced anti-tumor immune response. Oncolytic viruses and CAR-T therapies have shown promising results in recurrent glioma through multiple mechanisms. Vaccination strategies and immune-cell-based immunotherapies are promising in some subgroups of patients, and multiple new tumor antigenic targets have been discovered. In this review, we discuss current applicable immunotherapies and related mechanisms for recurrent glioma, focusing on multiple preclinical models and clinical trials in the last 5 years. Through reviewing the current combination of immune strategies, we would like to provide substantive thoughts for further novel therapeutic regimes treating recurrent glioma.

HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.

The 70 kDa heat shock proteins (HSP70s) are a group of highly conserved and inducible heat shock proteins. One of the main functions of HSP70s is to act as molecular chaperones that are involved in a large variety of cellular protein folding and remodeling processes. HSP70s are found to be over-expressed and may serve as prognostic markers in many types of cancers. HSP70s are also involved in most of the molecular processes of cancer hallmarks as well as the growth and survival of cancer cells. In fact, many effects of HSP70s on cancer cells are not only related to their chaperone activities but rather to their roles in regulating cancer cell signaling. Therefore, a number of drugs directly or indirectly targeting HSP70s, and their co-chaperones have been developed aiming to treat cancer. In this review, we summarized HSP70-related cancer signaling pathways and corresponding key proteins regulated by the family of HSP70s. In addition, we also summarized various treatment approaches and progress of anti-tumor therapy based on targeting HSP70 family proteins.

Complete dissection of right paratracheal lymph nodes (stations 2R and 4R) is critical to improve the prognosis of lung cancer patients: A retrospective cohort study.

BACKGROUND: The optimal extent of mediastinal lymph node dissection is still under debate. This study aimed to investigate the prognostic impact of complete dissection of right paratracheal lymph nodes (LNs) in right-sided non-small cell lung cancer (NSCLC) and evaluate the potential patient population who will particularly benefit from right paratracheal node dissection (RPND). METHODS: Between January 2009 and December 2019, we retrospectively reviewed 2650 patients with primary right-sided NSCLC who underwent pulmonary surgery with lymphadenectomy in the Western China Lung Cancer Database. A total of 2447 patients received both 2R and 4R LNs dissection (complete RPND group), 162 patients received only 2R or 4R LNs dissection (incomplete RPND group), and 41 patients received neither 2R nor 4R LNs dissection (no RPND group). Overall survival (OS) was analyzed. RESULTS: The metastasis rates in stations 2R and 4R were 6.5% and 8.0%, respectively. In stage N2 patients, the frequency of involvement of stations 2R/4R was 74.8%. The complete RPND group had a significantly better survival than the incomplete and no RPND group (5-year OS, 79.5% vs. 72.7% vs. 65.5%; p < 0.001). In the multivariate analysis, status of RPND (incomplete RPND vs. complete RPND: HR 1.45, 95% CI: 1.10-1.90; p = 0.009; no RPND vs. complete RPND: HR 2.25, 95% CI: 1.37 to 3.69; p = 0.001), age, gender, tumor size, histological type, pTNM stage, pT stage, pN stage, and adjuvant treatment were independent factors for OS. CONCLUSIONS: Complete RPND brings survival benefits to patients with right-sided NSCLC. We suggest complete RPND as a standard procedure for patients with right-sided NSCLC.

Targeted tissue proteomic analysis of human astrocytomas.

Complicating proteomic analysis of whole tissues is the obvious problem of cell heterogeneity in tissues, which often results in misleading or confusing molecular findings. Thus, the coupling of tissue microdissection for tumor cell enrichment with capillary isotachophoresis-based selective analyte concentration not only serves as a synergistic strategy to characterize low abundance proteins, but it can also be employed to conduct comparative proteomic studies of human astrocytomas. A set of fresh frozen brain biopsies were selectively microdissected to provide an enriched, high quality, and reproducible sample of tumor cells. Despite sharing many common proteins, there are significant differences in the protein expression level among different grades of astrocytomas. A large number of proteins, such as plasma membrane proteins EGFR and Erbb2, are up-regulated in glioblastoma. Besides facilitating the prioritization of follow-on biomarker selection and validation, comparative proteomics involving measurements in changes of pathways are expected to reveal the molecular relationships among different pathological grades of gliomas and potential molecular mechanisms that drive gliomagenesis.

Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.

Heat shock protein (HSP90), a highly conserved molecular chaperon, is indispensable for the maturation of newly synthesized poly-peptides and provides a shelter for the turnover of misfolded or denatured proteins. In cancers, the client proteins of HSP90 extend to the entire process of oncogenesis that are associated with all hallmarks of cancer. Accumulating evidence has demonstrated that the client proteins are guided for proteasomal degradation when their complexes with HSP90 are disrupted. Accordingly, HSP90 and its co-chaperones have emerged as viable targets for the development of cancer therapeutics. Consequently, a number of natural products and their analogs targeting HSP90 have been identified. They have shown a strong inhibitory effect on various cancer types through different mechanisms. The inhibitors act by directly binding to either HSP90 or its co-chaperones/client proteins. Several HSP90 inhibitors-such as geldanamycin and its derivatives, gamitrinib and shepherdin-are under clinical evaluation with promising results. Here, we review the subcellular localization of HSP90, its corresponding mechanism of action in the malignant phenotypes, and the recent progress on the development of HSP90 inhibitors. Hopefully, this comprehensive review will shed light on the translational potential of HSP90 inhibitors as novel cancer therapeutics.