[Treatment strategies for patients with resistant advanced breast cancer to CDK4/6 inhibitors].

CDK4/6 inhibitors have become the standard of care for HR-positive, HER2-negative advanced breast cancer. However, there is still a lack of standard recommendations for the subsequent treatment of patients with CDK4/6 inhibitor resistance, especially those with primary resistance or rapid progression. Currently, appropriate treatment strategies included re-challenge of CDK4/6 inhibitors, combination with PI3K/AKT/mTOR inhibitors, new antibody drug conjugate (ADC), novel endocrine therapy drugs, and chemotherapy. In addition, many new targeted drugs and new combination treatment strategies are also being explored. In the future, precise treatment strategies based on biomarkers should be established, as well as the optimal sequence of use of different therapies.

[Oligometastatic and oligoprogressive esophageal squamous cell carcinoma:clarifying conceptions and surgery perspectives].

The oligometastatic and oligoprogressive state has been a hot issue in cancer research. Its indolent tumor behavior, representing a novel therapeutic opportunity, has been identified as a clinical subtype in several malignancies. However, the clinical implications of the oligometastatic and oligoprogressive state in esophageal squamous cell carcinoma (ESCC) have not been thoroughly elucidated. There are still controversies regarding the existence of the oligometastatic state in ESCC, if the solitary regional lymph node metastasis should be viewed as oligoprogressive disease after esophagectomy, and the role of surgery and radiotherapy in ESCC oligometastatic disease. Despite many exciting contributions to the literature on these, further exploration is warranted. Thus, fostering the advance of research and scientific knowledge on the biological and prognostic characteristics scrupulously would facilitate personalizing treatment strategy for better outcomes.

Neuroprotection effect of interleukin (IL)-17 secreted by reactive astrocytes is emerged from a high-level IL-17-containing environment during acute neuroinflammation.

An increase in interleukin (IL)-17A-producing cells, particularly at sites of tissue inflammation, is observed frequently, yet the mechanism is not fully understood. This study aims to dissect the role of IL-17 in autoimmunity-mediated neuroinflammation. The cytokine milieu containing elevated IL-17, which often appears in active states of autoimmunity, was mimicked in vitro by a supernatant obtained from rat peripheral blood monocytes stimulated with phorbol mystistate acetate (PMA)/ionomycin. The application of such inflammatory media on only primary cultured cerebellar granule neurones resulted in significant apoptosis, but the presence of astrocytes largely prevented the effect. The supernatants of the stimulated astrocytes, especially those that contained the highest level of IL-17, achieved the best protection, and this effect could be blocked by anti-IL-17 antibodies. Protein IL-17 inhibited intracellular calcium increase and protected the neurones under inflammatory attack from apoptosis. IL-17, but not interferon (IFN)-γ, in the inflammatory media contributed to astrocyte secretion of IL-17, which depended on the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway activation. The astrocytes that were treated with IL-17 alone or with prolonged treatment of the inflammatory media failed to produce sufficient levels of IL-17. Moreover, confirmatory data were obtained in vivo in a monophasic experimental autoimmune uveitis (EAU) in Lewis rats; in this preparation, the high-level IL-17-containing the cytokine milieu was demonstrated, along with IL-17 secretion by the resident neural cells. The antagonism of IL-17 at a late stage disturbed the disease resolution and resulted in significant neural apoptosis. Our data show a dynamic role of IL-17 in the maintenance of homeostasis and neuroprotection in active neuroinflammation.

[Advances of immunotherapy-related biomarker in esophageal carcinoma].

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

[Changes of mitogen-activated protein kinase activity in cardiac tissues, Ang II and cardiac hypertrophy in spontaneously hypertensive rats].

Mitogen-activated protein kinases (MAPKs) are thought to be critical components in signal transduction pathways in regulation of cell growth and differentiation. The purpose of the present investigation is to study possible involvement of MAPKs in the progress of cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and effects of age on Angiotensin II (Ang II), MAPK activity and cardiac hypertrophy. The animals were divided into three groups: 4 months old WKY rats (n = 8), 4 month old SHRs (n = 8) and 15 month old SHRs (n = 6). Ratio of heart to body weight was measured. Ang II was determined by RIA. MAPK activity in cardiac tissue was assayed by the "in-gel" myelin basic protein phosphorylation. The results show that in comparison with 4 month old WKY rats, Ang II in plasma and cardiac tissues were elevated (216.4%, P < 0.01; 101.2%, P < 0.01) in 4 months old SHRs, while the MAPK activity was increased 107.0% (P < 0.01) with a parallel cardiac hypertrophy (P < 0.01). In comparison with 4 month old SHRs, Ang II and MAPK activity in cardiac tissue of the 15 months old SHRs were decreased (31.3%, P < 0.01; 29.7%, P < 0.05) but the cardiac hypertrophy increased by 38.5% (P < 0.01). MAPK may be involved in the progress of cardiac hypetrophy in SHR and the increased MAPK activity may be partly induced by Ang II.

A comparison of rest sestamibi and rest-redistribution thallium single photon emission tomography: possible implications for myocardial viability detection in infarcted patients.

Thirty patients (26 men, 4 women, mean age 61 +/- 8 years) who had suffered myocardial infarction 15 +/- 6 months previously, were submitted to (1) standard stress-redistribution thallium-201 single photon emission tomography (SPET), (2) rest-redistribution 201T1 SPET and (3) stress-rest technetium-99m sestamibi SPET. Uptake modifications in relation to exercise-induced defects were evaluated in a total of 390 myocardial segments. Tracer uptake was scored as normal (=0), mildly reduced (=1), apparently reduced (=2), severely reduced (=3) or absent (=4). Comparison of stress studies failed to show any statistical difference (58% segmental abnormalities with sestamibi vs 61% with thallium). Uptake abnormalities (score 1-4) were detected in 55% of the segments with sestamibi, 55% with standard thallium redistribution, 55% with early imaging after thallium injection at rest and 54% with 3-h delayed rest imaging (P = NS). Absence of tracer uptake (score = 4) under resting conditions was recorded in 75 (19%) segments with standard 201T1 redistribution, 75 (19%) with rest sestamibi, 70 (18%) with rest 201T1 imaging and 62 (16%) with rst-redistribuion 201T1 (P < 0.05 vs other imaging modalities). Thus, 3-h delayed rest thallium imaging detected reversibility of uptake defects in a significantly higher number of myocardial segments. This finding might have important implications for both tracer and technique selection when myocardial viability is the main clinical issue.