Cancer pathogenesis and therapy最新文献

The adaptive arm of the immune system is crucial for appropriate antitumor immune responses. It is generally accepted that clusters of differentiation 4⁺ (CD4⁺) T cells, which mediate T helper (Th) 1 immunity (type 1 immunity), are the primary Th cell subtype associated with tumor elimination. In this review, we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans, with a focus on Th2 cells. The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the (1) site of tumor development, (2) tumor properties (i. e., tumor metabolism and cytokine receptor expression), and (3) type of immune response that the tumor initially escaped. Therefore, we discuss how low-tolerance organs, such as lungs and brains, might benefit from a less tissue-destructive immune response mediated by Th2 cells. In addition, Th2 cells antitumor effects can be independent of CD8+ T cells, which would circumvent some of the immune escape mechanisms that tumor cells possess, like low expression of major histocompatibility-I (MHC-I). Finally, this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.

Background

Autologous hematopoietic stem cell (HSC) transplantation remains the recommended treatment for eligible patients with multiple myeloma (MM). Increasing the number of transplanted CD34⁺ cells shorten the time to hematopoietic reconstitution and increases the overall survival of patients. With the harvest of a sufficient CD34⁺ cell number being crucial, this study aimed to predict the factors that affect stem cell collection.

Methods

We conducted a retrospective study of 110 patients who were newly diagnosed with MM and underwent autologous HSC collection at Beijing Jishuitan Hospital between March 2016 and July 2022. Multiple factors were analyzed using the Mann–Whitney U tests for between-group comparisons. Differences were considered statistically significant at P ​< ​0.05.

Results

We found that patient age affected stem cell collection significantly; for patients younger than 55 years, the number of CD34+ cells harvested may be ​≥ ​2 ​× ​10⁶/L, is unlikely to reach 5 ​× ​10⁶/L. Platelet count at initial mobilization was a predictor of the number of CD34⁺ cells collected. Collection may fail when the platelet count at initial mobilization is below 177 ​× ​10⁹/L and may be excellent when it is higher than 199 ​× ​10⁹/L.

Conclusions

This finding could guide us to predict the approximate number of CD34⁺ cells collected in advance during autologous transplant mobilization for MM and to decide in advance whether to apply plerixafor to improve the number of HSCs collected.

Background

Freehand transperineal prostate biopsy (TPPBx) using a coaxial needle technique offers an alternative to probe-mounted freehand or template-guided techniques in the diagnosis of prostate cancer (PCa). It only requires the same equipment used for transrectal ultrasound-guided (TRUS) biopsy. Our study is the first in Malaysia to report this experience and its outcomes. We aim to determine PCa detection rate and pain tolerability of freehand TPPBx utilizing a coaxial needle under local anesthesia (LA).

Methods

Institutional review board approval was obtained from National Medical Research Register (NMRR ID-21-02052-VIL). We retrospectively reviewed the medical records of patients who underwent TPPBx between August 2020 and April 2022. Records were reviewed for patients’ characteristics, prostate volume, prostate-specific antigen (PSA) results, biopsy results and pain tolerability. Data was analyzed to determine PCa and clinically significant prostate cancer (csPCa) detection rate. LA was achieved using perineal skin infiltration and a periprostatic nerve block. The commonly used standard side-firing transrectal ultrasound with its Prostate Biplane Transducer was used as an imaging guide. The principles of the Ginsburg protocol were followed. Pain tolerability was assessed using a visual analog scale.

Results

A total of 55 patients with elevated PSA levels underwent freehand TPPBx under LA. The mean age was 67.3 years, the median PSA was 14.2 ng/mL, and the median PSA density (PSAD) was 0.33 ng/mL/cc. The optimal PSAD cutoff for predicting csPCa was 0.35 ng/mL/cc (area under the curve [AUC], 0.792; sensitivity, 87.5%; specificity, 69.2%). PCa was detected in 24 patients (43.6%), of whom 16 (29.1%) had csPCa. The median pain scores during LA infiltration and biopsy were four and two, respectively, which were significant different (P < 0.05). TPPBx exhibited an infection rate of zero.

Conclusion

The PCa detection rate and patient tolerability of freehand TPPBx using a coaxial needle are similar to those of a contemporary published series. The use of existing equipment that is used for TRUS biopsy allows for widespread use and transition from TRUS biopsy.

Even today, lung cancer remains one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Throughout the past decades, remarkable advances have been made in the research and development of anti-lung cancer drugs in China. Since the first registered Chinese clinical trial on May 2, 2006, many potent anti-lung cancer drugs have been developed and approved by the China Food and Drug Administration and the National Medical Product Administration of China. Among them, the most advance were observed in the development of targeted agents and immunotherapeutic agents such as epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) icotinib, aumolertinib, and furmonertinib, anaplastic lymphoma kinase (ALK)-TKI ensartinib, programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) camrelizumab, sintilimab, and tislelizumab, and programmed cell death-ligand 1 (PD-L1) mAb sugemalimab, which have made huge breakthrough in recent years. Some other investigational innovative drug also demonstrated promising efficacy and acceptable safety profiles. Results from clinical studies on these China innovative drugs have led to changes in clinical practice guidelines and considerably improved the outcomes for patients with lung cancer. Thus, in this review, we aim to provide further insight into the clinical development and achievement of China innovative anti-lung cancer drugs.

Small cell lung cancer (SCLC) is a highly aggressive tumor type for which limited therapeutic progress has been made. Platinum-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment, but most patients with SCLC acquire therapeutic resistance. Given the need for more effective therapies, better elucidation of the molecular pathogenesis of SCLC is imperative. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid tumors. This pathway is an important regulator of cancer cell glucose metabolism, and its activation probably effects radioresistance by influencing bioenergetic processes in SCLC. Glucose metabolism has three main branches—aerobic glycolysis, oxidative phosphorylation, and the pentose phosphate pathway—involved in radioresistance. The interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1 (HIF-1) signaling. The PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radioresistance, including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate pathway. This review summarizes our understanding of links among the PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.

Background

A hepatic adverse event (HAE) is defined as a liver injury that occurs following immune checkpoint inhibitor (ICI) administration in oncology Patients. Immune-mediated hepatotoxicity (IMH) is a type of HAE directly caused by ICI and is associated with immune system hyperactivation. HAE incidence varies across different clinical studies. This study aimed to explore the risk factors of HAE and establish a personalized IMH treatment strategy.

Methods

Randomized controlled trials (RCTs) on ICIs and case reports related to IMH were collected and summarized separately. Meta-analysis was performed using Review Manager (version 5.0), whereas correlation analysis and linear regression were performed using SPSS (version 24.0) to evaluate any correlations between the two variables.

Results

Overall, 36 RCTs containing 18,515 patients and 39 case reports met our inclusion criteria. The ICI administration increased the HAE risk (risk ratio [RR] ​= ​1.40) as well as severe HAE (RR ​= ​2.55). The overall HAE incidence and severe incidence were about 15.3% and 4.3%, respectively. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors have a higher incidence of HAE than programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. Finally, we found a positive correlation between the onset time of IMH and the recovery time of liver injury.

Conclusions

ICI administration increased the incidence risk of HAE, especially in patients treated with CTLA-4 inhibitors. Regarding IMH treatment, the glucocorticoid dosage must be individually reduced according to the severity and onset time of HAE.