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.

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.

Background: Prolonged air leak (PAL) is one of the most common postoperative complications after pulmonary resection. The aim of this study was to reveal the incidence and risk factors of PAL in video-assisted thoracic surgery (VATS) lung cancer resection, and to evaluate the effect of PAL on postoperative complications, postoperative length of stay (PLOS), and medical costs. Methods: Continuous patients who underwent VATS major pulmonary resection for lung cancer between January 2014 and December 2015 were studied. Clinical data of these patients were obtained from the Western China Lung Cancer Database. PAL was defined as air leak more than 5 days after surgery. The risk factors for PAL were analyzed, as well as the effect of PAL on postoperative clinical recovery. Results: A total of 1,051 patients were enrolled in this study. The incidence of PAL was 10.6% (111/1,051). Pleural adhesion [odds ratio (OR), 2.38 for extensive vs. none, P=0.001] was identified as the only independent risk factors for PAL through multivariate analysis. The incidence of overall complications and pneumonia were significantly higher in patients with PAL (PAL group) than those without PAL (non-PAL group) (OR, 6.77, P=0.000; OR, 2.41, P=0.010, respectively). PAL was found to be associated with longer PLOS (11.7±6.6 vs. 6.5±3.6 days; P=0.000) and higher medical costs (¥62,042.5±18,072.0 vs. ¥52,291.3±13,845.5, P=0.000). Conclusions: Pleural adhesion was associated with increased risk of PAL after VATS lung cancer resection. Those patients with PAL had more postoperative complications, stayed longer in the hospital after surgery, and paid higher medical costs.

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.

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.