Long-term Survival Of Cancer Patients Research Articles

Method Development for Sorting Immune Cell Populations Within Tertiary Lymphoid Structures.

The tumor microenvironment is a complex network of interacting cells composed of immune and nonimmune cells. It has been reported that the composition of the immune contexture has a significant impact on tumor growth and patient survival in different solid tumors. For instance, we and other groups have previously demonstrated that a strong infiltration of T-helper type 1 (Th1), memory CD8+ T cells, and immune cells organized into tertiary lymphoid structures is associated with the long-term survival of cancer patients. Nevertheless, the prognostic value of the other immune populations, namely regulatory T cells (Treg), B cells, and gamma-delta (γδ) T cells remains a matter of debate. Herein, we describe novel flow cytometry-based strategies to sort out these different immune populations to evaluate their role in non-small-cell lung cancer (NSCLC).

TMET-24. MULTI-OMIC CHARACTERIZATION OF THE TEMPORAL METABOLIC ADAPTATIONS UNDERPINNING THERAPY RESISTANCE AND TUMOR RECURRENCE IN GLIOBLASTOMA

Abstract Therapy resistance and tumor recurrence are barriers to achieving long-term survival in cancer patients, particularly evident in glioblastoma (GBM), known for its dismal 5-year survival rate below 10%. Despite aggressive treatment regimens, including maximal resection, alkylating chemotherapy, and radiation, the majority of GBM patients experience relapse within 7-9 months post-initial intervention. Recurrent GBM poses surgical challenges and resists subsequent treatments, leading to an almost universally fatal outcome and an average survival of 12-18 months. Metabolic networks can serve as ancient stress-protection mechanisms that operate independently of genomic changes, offering an initial line of defense against exogenous pressures. Although the role of metabolism in cancer has gained prominence, our understanding of the metabolic adaptations following chemoradiotherapy and their contributions to therapy resistance and tumor recurrence in highly aggressive GBM tumors remains incomplete. We postulate that metabolic adaptations play a pivotal role in facilitating therapy resistance and GBM recurrence. Exploring the metabolic dependencies of these persistent cells may unveil vulnerabilities for therapeutic exploitation to counteract chemoradiotherapy resistance. We established clinically relevant patient-derived in vitro and in vivo models mirroring the standard GBM treatment protocol. Using state-of-the-art single-cell and bulk multi-omics technologies, we profiled the temporal transcriptomic and metabolomic adaptations from therapy-naïve primary GBM to chemoradiotherapy-resistant recurrent tumors. Our findings revealed unique metabolic transitions that occurred during chemoradiotherapy treatment in GBM cells that were conserved in vitro and in vivo across ten genetically diverse GBM patients. In a pre-clinical animal trial, a novel metabolism-targeting combinatorial treatment regimen prevented the emergence of recurrent tumors and significantly prolonged survival compared to chemoradiotherapy alone. Altogether, our results uncover distinct metabolic adaptations mediating therapy resistance and tumor recurrence in GBM. These findings emphasize the need to consider metabolic flexibility and dependencies for effective therapeutic strategies, offering potential avenues to overcome chemoresistance in recurrent GBM tumors.

CBioProfiler: A Web and Standalone Pipeline for Cancer Biomarker and Subtype Characterization.

Cancer is a leading cause of death worldwide, and the identification of biomarkers and subtypes that can predict the long-term survival of cancer patients is essential for their risk stratification, treatment, and prognosis. However, there are currently no standardized tools for exploring cancer biomarkers or subtypes. In this study, we introduced Cancer Biomarker and subtype Profiler (CBioProfiler), a web server and standalone application that includes two pipelines for analyzing cancer biomarkers and subtypes. The cancer biomarker pipeline consists of five modules for identifying and annotating cancer survival-related biomarkers using multiple survival-related machine learning algorithms. The cancer subtype pipeline includes three modules for data preprocessing, subtype identification using multiple unsupervised machine learning methods, and subtype evaluation and validation. CBioProfiler also includes CuratedCancerPrognosisData, a novel R package that integrates reviewed and curated gene expression and clinical data from 268 studies. These studies cover 43 common blood and solid tumors and draw upon 47,686 clinical samples. The web server is available at https://www.cbioprofiler.com/ and https://cbioprofiler.znhospital.cn/CBioProfiler/, and the standalone app and source code can be found at https://github.com/liuxiaoping2020/CBioProfiler.

Perioperative blood transfusions associated with reduced survival in gastroesophageal cancers – A Swedish population-based study

BackgroundBlood transfusion has been associated with decreased long-term survival in cancer patients, possibly due to various immunological factors. We aimed to evaluate if perioperative transfusions decrease survival in patients who undergo resection for esophageal or gastric cancer and to identify factors associated with such events. MethodsA population-based cohort study was conducted based on the Swedish National Registry for Esophageal and Gastric Cancer, which prospectively collects clinical data of patients with these tumors. Almost all patients (96 %) resected for esophageal or gastric cancer in Sweden between 2017 and 2022 were included. Survival data were acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), adjusted for age, fitness, neoadjuvant therapy, surgical access, and pathological TNM stage. ResultsOf all 1365 patients, 227 (17 %) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (adjusted HR 1.50, 95 % CI 1.17–1.91). To exclude the influence of surgery-related postoperative complications, a sensitivity analysis was performed excluding patients who died within 30 days of resection and the negative impact of transfusions on 3-year mortality remained (adjusted HR 1.30, 95 % CI 1.01–1.68). Increasing age, open surgery, esophagectomy, perioperative bleeding, and nodal tumor involvement were all associated with an increased likelihood of receiving transfusions. ConclusionPerioperative blood transfusions might have a negative impact on 3-year survival in patients who undergo surgery for esophageal or gastric cancer.

273. PERIOPERATIVE BLOOD TRANSFUSIONS AND SURVIVAL IN GASTROESOPHAGEAL CANCERS – A SWEDISH POPULATION-BASED STUDY

Abstract Background Blood transfusions have been associated with decreased long-term survival in cancer patients, possibly due to immunological factors. This cohort study aimed to investigate associations, if any, between perioperative transfusions and survival in gastroesophageal cancer patients. Methods A population-based cohort study was conducted based on the National Registry for Esophageal and Gastric cancer (NREV), which harbors clinical data including given transfusions. All patients resected for esophageal or gastric cancer in Sweden, between 2017 and 2022, were included and their survival was acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders (age, American Society of Anesthesiologist class, access of surgery and pathological TNM stage) Results Of 1,368 patients, 227 patients (17%) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (HR 1.48 95% CI 1.17-1.91). Kaplan-Meier curves depicted worse crude survival in patients having received peroperative transfusion (Figure 1). To exclude the effects of surgery-related postoperative complications on short-term mortality, a sensitivity analysis was performed, excluding patients who died within 30 days of resection, and found that the impact of transfusions on survival remained. Conclusion Perioperative blood transfusions might have a negative impact on survival in patients who undergo gastroesophageal cancer surgery.

Long-term survival of cancer patients after photobiomodulation therapy for prevention and treatment of oral mucositis

BackgroundPhotobiomodulation therapy (PBMT) has been employed for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing treatment. However, information about the survival of patients receiving PBMT is still lacking. Therefore, the aim of this study was to correlate the survival of patients who either received or did not receive PBMT, combined with cancer treatments, and to assess whether the number of PBMT sessions had a positive impact on survival. MethodsThe records of 751 patients seen at Hospital de Caridade São Vicente de Paulo diagnosed with head and neck cancer, treated by D.L.P., the sole operator of PBMT, between 2000 and 2016, were analyzed. The median survival rates were compared by analyzing diagnostic staging, the combination of cancer treatments, and the number of PBMT sessions. Correlation analyses were performed to assess the interactions between the number of PBMT sessions and survival. ResultsPBMT increased survival by 55.14 %, from 1.07 (Without PBMT) to 1.66 years (With PBMT) for the total population and more significantly in Group 41 (stages III and IV, radiation therapy/chemotherapy, with more than five PBMT sessions), the median survival value of 1.83 years, which represents a 66.36 % higher survival rate. In all the analyzed populations, the larger number of sessions was associated with better survival. In terms of survival, advanced stages III and IV almost equated with stages I and II in the absence of PBMT. ConclusionsPBMT seems to interfere with the survival of patients with head and neck cancer, corroborating its recommendation for the treatment of mucositis, but further research is needed to investigate possible synergistic effects between PBMT and cancer treatments.

Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study

BackgroundHepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia.MethodsThis multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL).ResultsC-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19–1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25–1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels.ConclusionLow albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.

Current issues of post-covid syndrome consequences

Background. The World Health Organization (WHO) has confirmed the outbreak of covid infection and defined it as a global pandemic. Recently, complications have been increasingly reported in patients who have had COVID-19. At the same time, clinical symptoms of the long-term course of this disease overlap, differing from acute manifestations of the infection, and may persist in recovered patients for several weeks, months or years, adding a number of other problems. Therefore, the importance of a thorough study of the post-COVID-19 syndrome as a modern phenomenon has increased. And this syndrome requires proper research to improve the efficiency of its prevention and treatment. &#x0D; Purpose. To evaluate the current state of the problem of post-COVID-19 syndrome, in particular in cancer patients.&#x0D; Materials and methods. A literature review was performed based on the array of digital publications found in the world databases PubMed, Scopus and Web of Science Core Collection for 2020–2023. The sources were systematized in separate groups, i.e., issues related to post-Covid, in particular, the mechanisms and pathogenesis of its development; treatment features, including cancer patients; long-term consequences in recovered patients, etc.&#x0D; Results and discussion. The terminology on the subject of the study has been analyzed: post-COVID, post-COVID syndrome, PASC, long-COVID, acute COVID, chronic COVID, etc. The views regarding the pathogenesis of post-COVID syndrome and its main symptoms were systematized. It is determined that in the field of oncology, research is conducted in certain fields and the risk of progression and occurrence of cancer in the post-COVID period is evaluated; the efficiency of the process of cancer care organization in the post-COVID period and the level of complications and mortality of cancer patients who have suffered from COVID-19. The pandemic has also led to multiple changes in the field of radiological diagnosis of the consequences of cancer patients with COVID. Evaluating the impact of the pandemic on the outcomes and adaptation of radiotherapy and chemotherapy, it was determined that delays in the provision of timely care and changes in treatment regimens will affect long-term survival of cancer patients.&#x0D; Conclusion. Assessing the current state of the problem of post-COVID syndrome, most researchers believe that cancer progression during delay in cancer care will negatively affect the long-term survival of cancer patients, and coincidence of cancer-related symptoms and symptoms of long-term COVID is another major challenge for oncologists in the future.

Long-Term Survival in Patients with Cancers: Surveillance, epidemiology and end results-based analysis.

This study aimed to explore real-world data on the long-term survival of cancer patients using historical records from the Surveillance, Epidemiology, and End Results (SEER) Programme. Long-term survival is an important endpoint in the management of different malignancies. It is rarely assessed due to the unfeasibility of follow-up for a long duration of time. Besides reporting the five-year relative survival, the 10- and 20-year survival rates for different types of cancers were analysed. Additionally, survival trends as a function of time, age and tumour type were reviewed and reported. The study used SEER*Stat (Version 8.3.6.1) for data acquisition from the SEER 9 Regs (November 2019) database. Data from patients diagnosed with cancer between 1975 and 2014 were retrieved and included in the analysis. For patients diagnosed with any malignant disease (N = 4,412,024), there was a significant increase in median overall survival over time (P <0.001). The 20-, 10-, and 5-year survival rates were higher in solid tumours compared to haematological malignancies (50.8% versus 38%; 57% versus 47.4%; and 62.2% versus 57.4%, respectively). The highest 20-year relative survival rates were observed in thyroid cancer (95.2%), germ cell and trophoblastic neoplasms (90.3%), melanoma (86.8%), Wilms' tumour (86.2%) and prostate cancer (83.5%). Long-term follow-up data were suggestive of high 20-year relative survival rates for most tumour types. Relative survival showed an improving trend over time, especially in solid tumours.

Glioblastoma Metabolism: Insights and Therapeutic Strategies.

Tumor metabolism is emerging as a potential target for cancer therapies. This new approach holds particular promise for the treatment of glioblastoma, a highly lethal brain tumor that is resistant to conventional treatments, for which improving therapeutic strategies is a major challenge. The presence of glioma stem cells is a critical factor in therapy resistance, thus making it essential to eliminate these cells for the long-term survival of cancer patients. Recent advancements in our understanding of cancer metabolism have shown that glioblastoma metabolism is highly heterogeneous, and that cancer stem cells exhibit specific metabolic traits that support their unique functionality. The objective of this review is to examine the metabolic changes in glioblastoma and investigate the role of specific metabolic processes in tumorigenesis, as well as associated therapeutic approaches, with a particular focus on glioma stem cell populations.

Detection of missed deaths in cancer registry data to reduce bias in long-term survival estimation.

Population-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population. We analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population. For the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined. The method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.

Cardio-Protection Against Cancer Treatment-Related Cardiac Dysfunction: Who is at Risk?

Long-term survival of cancer patients has improved, and the sequelae of treatment have become more evident. Mortality rates of cancer patients, adjusted for age, have decreased globally, with a reduction by 17% from 1990 to 2019. The prevention of left ventricular dysfunction secondary to cancer treatment is still a medical challenge. Drug-induced cardiotoxicity is the main limiting factor for the administration of higher doses of anthracyclines. Addressing the anthracycline-induced cardiotoxicity is particularly important for pediatric cancer survivors, as it remains [...]

Translation Potential and Challenges of In Vitro and Murine Models in Cancer Clinic

As one of the leading causes of death from disease, cancer continues to pose a serious threat to human health globally. Despite the development of novel therapeutic regimens and drugs, the long-term survival of cancer patients is still very low, especially for those whose diagnosis is not caught early enough. Meanwhile, our understanding of tumorigenesis is still limited. Suitable research models are essential tools for exploring cancer mechanisms and treatments. Herein we review and compare several widely used in vitro and in vivo murine cancer models, including syngeneic tumor models, genetically engineered mouse models (GEMM), cell line-derived xenografts (CDX), patient-derived xenografts (PDX), conditionally reprogrammed (CR) cells, organoids, and MiniPDX. We will summarize the methodology and feasibility of various models in terms of their advantages and limitations in the application prospects for drug discovery and development and precision medicine.

Impact of whole thorax irradiation on cardiac remodeling and outcome after ischemia/reperfusion

Abstract Background Thoracic irradiation is a fundamental treatment of several malignancies and has contributed to significant rise in long-term survival of cancer patients. However, a potentially increased risk of cardiac late effects, such as accelerated atherosclerosis, coronary heart disease or myocardial fibrosis, may partially diminish the therapeutic benefit and increase the risk of cardiovascular events, e.g. ischemia/reperfusion (I/R). The purpose of this project was to unravel the impact of whole thorax irradiation (WTI) on the outcome and cardiac remodeling after I/R. Method 11-week-old male C57BL/6J mice were either exposed to WTI with a single dose (12.5 Gy) or sham-irradiation only (0 Gy) and subsequently observed over four weeks. Blood samples were taken to monitor early changes in circulating leukocytes (flow cytometry) and RNA was isolated from cardiac tissue to observe damage to mitochondria by analysis of different mitochondrial markers. To study the impact of WTI on cardiac remodeling and outcome after I/R, mice were subjected to ischemia by occlusion of the left anterior descending artery (for 45 minutes) four weeks after WTI or sham-irradiation, followed by reperfusion for up to three weeks. During early timepoints of cardiac remodeling, circulating immune cells and the immune cell influx in the heart were analysed (flow cytometry), ischemic area and cardiac inflammation were assessed by magnetic resonance imaging (MRI) and multiple cytokines were measured in the plasma (immunoassay). Results After WTI, a downregulation of leukocyte numbers was observed three days after irradiation, which recovered over four weeks. In addition, WTI resulted in a decrease in relative mRNA expression of mitochondrial fission factor (MFF) and a decrease in relative ATP levels in irradiated mice, suggesting damage of cardiac mitochondria. The combined setup of WTI and I/R led to enhanced plasma concentration of IL-12(p70), IL-13, MCP-1 or MIP-1β and an increased ischemic area one day after I/R. Further, cardiac inflammation was increased three days post I/R in irradiated mice. Flow cytometric analysis revealed, increased amounts of circulating Ly6Chigh monocytes (% of all monocytes) and cardiac myeloid cells, specifically macrophages. Survival of irradiated mice was impaired already after one week post I/R; therefore, when analysing scar size three weeks later, no changes could be observed in the surviving mice. Conclusion Our data show that WTI causes early damage to cardiac mitochondrial network. While WTI also led acutely to a decrease in circulating immune cells, upon I/R, the preexisting irradiation-induced cardiac damage impacts on circulating and cardiac macrophages and monocytes resulting in increased cardiac inflammation and plasma concentration of cytokines in irradiated mice. In sum, irradiation-induced cardiac damage and subsequently altered immune response are likely contributing to the impaired survival of irradiated mice after I/R. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG - GRK 1739

Effect of Perioperative Interleukin-6 and Tumor Necrosis Factor-α on Long-Term Outcomes in Locally Advanced Gastric Cancer: Results from the CLASS-01 Trial.

Background Little is known about the relation between perioperative inflammatory changes and long-term survival in cancer patients. The aim of the study was to assess the association of perioperative serum interleukin-6 (IL6) and tumor necrosis factor-α (TNFα) levels with the 5-year overall survival in locally advanced gastric cancer. Methods The 135 eligible patients in one center of Nanfang Hospital were retrieved from CLASS-01 trial (NCT01609309), an open-label, multicenter, randomized clinical noninferiority trial conducted at 14 centers in China. Serum IL6 and TNFα levels were tested before surgery, and on postoperative day (POD) 1, POD3, and POD5, respectively, referring to IL6_0, IL6_1, IL6_3, and IL6_5 and TNFα_0, TNFα_1, TNFα_3, and TNFα_5. Kaplan-Meier methods and COX models were used for survival analysis. Results High levels of IL6_0 (≥3.67 pg/mL) and TNFα_0 (≥14.8 pg/mL) presented worse disease-free survival (DFS) (P = 0.0057 for IL6_0 and P = 0.0014 for TNFα_0) and overall survival (OS) (P = 0.0021 for IL6_0 and P = 0.0019 for TNFα_0). Both high IL6_0 and high IL6_5 levels indicated worse prognosis than other combinations (P = 0.0045 for DFS and P = 0.0022 for OS). In multivariate analysis, both high IL6_0 and high IL6_5 levels were significantly associated with poor DFS (HR = 4.29, 95% CI: 1.42-12.95, P = 0.01) and OS (HR = 4.11, 95% CI: 1.35-12.49, P = 0.013) after adjustment of tumor stage and TNFα_0. Also, high IL6_5 level was identified as the independent-related factor for postoperative infectious complications (OR = 2.69, 95% CI: 1.03-7.01, P = 0.043). Conclusions Perioperative high serum IL6 and TNFα levels are negatively associated with 5-year survival outcomes in patients with locally advanced gastric cancer, indicating the potential survival benefits from perioperative anti-inflammatory treatment.

New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis.

Simple SummaryToday, the vast majority of deaths from cancer are due to cancer metastasis. Metastasis requires that cancer cells escape from the initial tumor, travel through blood vessels, and form new tumors in distant host tissues. Integrin-linked kinase (ILK) is overexpressed by many types of cancer cells and provides both structural and signaling functions that are important for successful metastasis. Here, we discuss recent findings that show how ILK is involved in promoting physical changes important for cell motility and invasion, and how ILK relays signals to other machinery components during metastasis, including interactions with components of the immune system and communication between cancer cells and normal cells, to affect the process of metastasis. We also discuss the contribution of ILK to therapeutic resistance and examine efforts to target ILK for the treatment of metastatic disease.Cancer metastasis is a major barrier to the long-term survival of cancer patients. In cancer cells, integrin engagement downstream of cell-extracellular matrix (ECM) interactions results in the recruitment of cytoskeletal and signaling molecules to form multi-protein complexes to promote processes critical for metastasis. One of the major functional components of these complexes is Integrin Linked Kinase (ILK). Here, we discuss recent advances in our understanding of the importance of ILK as a signaling effector in processes linked to tumor progression and metastasis. New mechanistic insights as to the role of ILK in cellular plasticity, epithelial mesenchymal transition (EMT), migration, and invasion, including the impact of ILK on the formation of invadopodia, filopodia-like protrusions (FLPs), and Neutrophil Extracellular Trap (NET)-induced motility are highlighted. Recent findings detailing the contribution of ILK to therapeutic resistance and the importance of ILK as a potentially therapeutically tractable vulnerability in both solid tumors and hematologic malignancies are discussed. Indeed, pharmacologic inhibition of ILK activity using specific small molecule inhibitors is effective in curtailing the contribution of ILK to these processes, potentially offering a novel therapeutic avenue for inhibiting critical steps in the metastatic cascade leading to reduced drug resistance and increased therapeutic efficacy.

Comparison of absolute and relative handgrip strength to predict cancer prognosis: A prospective multicenter cohort study

Decreased muscle strength, as measured by absolute handgrip strength (HGS), is associated with poor outcomes in patients with cancer. The ability of HGS to predict cancer prognosis may be affected by its absolute or relative representation. It is not clear whether absolute or relative HGS is more appropriate for the prognostic assessment of cancer. We conducted a multicenter prospective cohort study of 16,150 cancer patients. The exposure variables were absolute and relative HGS values. Relative HGS was standardized according to height, weight, body mass index (BMI), and mid-arm circumference (MAC). The Cox proportional hazard regression model was used to determine the relationship between HGS-related indices and survival. Logistic regression analysis was used to assess the association between HGS-related indices and 90-day outcomes. Both absolute and relative HGS were independent prognostic factors for cancer. All HGS-related indices are applicable to lung and colorectal cancer. Both absolute and MAC-adjusted HGS are applicable for breast cancer. For the prognostic assessment of hepatobiliary and urologic cancers, only height-adjusted HGS is applicable. Compared with absolute HGS, height-adjusted HGS had a better prediction performance (0.007; 95% CI, 0.006, 0.008; log-rank P<0.001), particularly in lung and colorectal cancer. However, the prediction performance of weight/BMI/MAC-adjusted HGS was worse than that of absolute HGS by (-0.015; 95% CI,-0.020,-0.011; log-rank P<0.001), (-0.028; 95% CI,-0.033,-0.023; log-rank P<0.001), and (-0.019; 95% CI,-0.022,-0.016; log-rank P<0.001), respectively. Low absolute and relative HGS were significantly associated with poor 90-day outcomes in patients with cancer. Height-adjusted HGS was better than absolute HGS in predicting 90-day outcomes, particularly in lung cancer. Among the HGS-related indices, height-adjusted HGS has an optimal value in predicting the short- and long-term survival of cancer patients, especially those with lung cancer.

Marine Migrastatics: A Comprehensive 2022 Update.

Metastasis is responsible for the bad prognosis in cancer patients. Advances in research on metastasis prevention focus attention on the molecular mechanisms underlying cancer cell motility and invasion to improve therapies for long-term survival in cancer patients. The so-called “migrastatics” could help block cancer cell invasion and lead to the rapid development of antimetastatic therapies, improving conventional cancer therapies. In the relentless search for migrastatics, the marine environment represents an important source of natural compounds due to its enormous biodiversity. Thus, this review is a selection of scientific research that has pointed out in a broad spectrum of in vitro and in vivo models the anti-cancer power of marine-derived products against cancer cell migration and invasion over the past five years. Overall, this review might provide a useful up-to-date guide about marine-derived compounds with potential interest for pharmaceutical and scientific research on antimetastatic drug endpoints.

Glycosylation in cancer: its application as a biomarker and recent advances of analytical techniques.

Despite significant worldwide investment in research, cancer remains one of the most common cause of death in the world. Early detection and reliable diagnosis are the keys to effectively treating cancer and improving the long-term survival of cancer patients. Therefore, there is an urgent need to develop a single, non-invasive biomarker with high sensitivity and specificity. Aberrant glycosylation is well defined as a hallmark of cancer and represents a promising source of potential biomarkers. Tumor-associated carbohydrate epitopes have long been detected by using monoclonal antibodies and lectins. Recent advances in analytical technologies allow us to analyze cancer-specific glycoforms on a target protein in a variety of clinical samples. A number of glycan analysis techniques, such as lectin-based detection methods and mass spectrometry combined with various types of chromatography, have been developed to establish novel glycoform-specific cancer biomarkers. Several glycan-based cancer biomarkers are already in clinical use. The aim of this review is to outline the role of glycan as a cancer biomarker and to summarize the current status and the potential for contribution of the serum glycoproteome to cancer diagnostics, monitoring, and prognostics.

Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer.

Previously regarded as simple fat storage particles, new evidence suggests that lipid droplets (LDs) are dynamic and functional organelles involved in key cellular processes such as membrane biosynthesis, lipid metabolism, cell signalling and inflammation. Indeed, an increased LD content is one of the most apparent features resulting from lipid metabolism reprogramming necessary to support the basic functions of cancer cells. LDs have been associated to different cellular processes involved in cancer progression and aggressiveness, such as tumorigenicity, invasion and metastasis, as well as chemoresistance. Interestingly, all of these processes are controlled by a subpopulation of highly aggressive tumoral cells named cancer stem cells (CSCs), suggesting that LDs may be fundamental elements for stemness in cancer. Considering the key role of CSCs on chemoresistance and disease relapse, main factors of therapy failure, the design of novel therapeutic approaches targeting these cells may be the only chance for long-term survival in cancer patients. In this sense, their biology and functional properties render LDs excellent candidates for target discovery and design of combined therapeutic strategies. In this review, we summarise the current knowledge identifying LDs and CSCs as main contributors to cancer aggressiveness, metastasis and chemoresistance.