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Purpose: This study aimed (1) to estimate the prevalence of cognitive frailty, (2) to identify factors associated with cognitive frailty and (3) to examine the association of cognitive frailty with health-related quality of life (HRQOL) in older cancer survivors., Methods: This was a cross-sectional study. Participants were aged 65 or above, diagnosed with cancer and had completed cancer treatment. Measures on physical frailty, cognitive functioning and HRQOL were administered. Multiple linear regression models were used to examine the association of cognitive frailty with HRQOL., Results: Among 293 recruited participants, 18.8% had a cognitive functioning decline, 8.9% were physically frail and 8.2% were cognitively frail. Regular exercise (OR = 0.383, p = .035) and shorter time since treatment completion were associated with less likelihood of cognitive frailty (OR = 1.004, p = .045). Cognitive frailty was significantly associated with global health status (β = -0.116; p = .044), physical functioning (β = -0.177; p = .002), social functioning (β = -0.123; p = .035) and fatigue symptoms (β = 0.212; p < .001) after adjusting for potential confounding variables., Conclusions: Cognitive frailty, found in 8.2% of older cancer survivors, is associated with various dimensions of HRQOL. Longitudinal research examining the trajectory and impact of cognitive frailty on more diverse health outcomes in older cancer survivors is warranted. The findings improve service providers' knowledge of cognitive frailty in older cancer survivors and inform surveillance and care for geriatric cancer survivorship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Study Objectives: To examine the trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment and to investigate whether psychological, cognitive, and physical factors differentiate trajectories., Methods: A total of 623 Chinese cancer survivors of diverse cancer types participated in a 2-year-long prospective study after the completion of cancer treatment. Sleep disturbance was measured using Pittsburgh Sleep Quality Index at 3 (T2), 6 (T3), 12 (T4), 18 (T5), and 24 (T6) months after baseline (within 6-months post-treatment; T1). Latent growth mixture modeling identified distinctive sleep disturbance trajectories and tested if these longitudinal patterns were predicted by baseline psychological distress, attentional control, attentional bias and physical symptom distress and T2 cancer-related distress. Fully adjusted multinomial logistic regression then identified whether these factors differentiated trajectories., Results: Two distinct sleep disturbance trajectories were identified, namely stable good sleepers (69.7%) and persistent high sleep disturbance (30.3%). Compared to those in the stable good sleep group, patients in the persistent high sleep disturbance group were less likely to report avoidant (OR=0.49, 95% CI = 0.26-0.90), while more likely to report intrusive thoughts (OR = 1.76, 95% CI = 1.06-2.92) and cancer-related hyperarousal (OR = 3.37, 95% CI = 1.78-6.38). Higher depression scores also predicted persistent high sleep disturbance group membership (OR = 1.13, 95% CI = 1.03-1.25). Attentional bias, attentional control, anxiety, and physical symptom distress did not predict sleep trajectory membership., Conclusions: One in three cancer survivors experienced persistent high sleep disturbance. Screening and managing depressive symptoms and cancer-related distress in early cancer rehabilitation may reduce risk of persistent sleep disturbance among cancer survivors., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Both acupuncture and acupressure have been suggested beneficial for reducing sleep disturbance in cancer patients. While acupuncture is invasive involving needle insertion, acupressure is noninvasive. Their comparative effectiveness is unclear, hindering clinical recommendations., Aims: This study aimed to explore the comparative effectiveness of acupuncture and acupressure on sleep in cancer patients., Methods: This is a systematic review and Bayesian network meta-analysis. Eight key English and Chinese databases were searched. Twenty-four randomized controlled trials involving 2002 cancer patients comparing the effects of six treatments (manual acupuncture, electroacupuncture, acupressure, sham, enhanced usual care, and no treatment) on sleep were found., Results: Compared with enhanced supportive care, acupressure demonstrated the largest effect size for reducing self-reported sleep disturbance (standardized mean difference [SMD] = -2.67, 95% CrI: -3.46 to -1.90; GRADE = moderate), followed by acupuncture (SMD = -1.87, 95% CrI: -2.94 to -0.81, GRADE = moderate) and electroacupuncture (SMD = -1.60, 95% CrI: -3 to -0.21; GRADE = low). The surface under the cumulative ranking curve indicates that acupressure is most likely to rank highest., Linking Evidence to Action: Based on available evidence, acupressure can be recommended as the optimal treatment for reducing sleep disturbance in cancer patients. More rigorous trials are warranted to confirm whether different forms of acupuncture or acupressure have different effects on sleep in cancer patients. Particularly, studies examining acupuncture interventions alone instead of in combination with other therapies are needed., (© 2022 Sigma Theta Tau International.)

Aims: The Cancer Health Literacy - 30 (CHLT-30) and Cancer Health Literacy - 6 (CHLT-6) are widely used instruments to measure cancer health literacy and to identify individuals with limited cancer health literacy, respectively. This study evaluated the psychometric performance of both instruments in Chinese cancer patient population., Methods: The back-translation method was used in cross-cultural adaptation. Chinese versions, labeled as CHLT-30-Chinese and CHLT-6-Chinese, were administered to a diverse cross-sectional sample of 602 cancer patients. Of these, 30 patients retook the instruments over a 2-week interval to estimate test-retest reliability. Classical and modern psychometric methods were used to estimate the item and test properties., Results: Model fit statistics confirmed the original measurement structures of CHLT-30-Chinese (one-factor model) and CHLT-6-Chinese (latent class model with limited and adequate cancer health literacy classes) providing construct validity evidence. The CHLT-30-Chinese showed high internal consistency (Cronbach's α = 0.83; McDonald's Ω = 0.93) and 2-week test-retest reliability (r = 0.78). The CHLT-6-Chinese separated limited and adequate cancer health literacy classes well (entropy = 0.77) with the estimated prevalence rates of 19% and 81%, respectively. The CHLT-6-Chinese was highly precise in assigning cancer patients into two categories: limited and adequate cancer health literacy classes with probability of 0.95 and 0.90, respectively. Invariant measurement properties of both instruments were supported between male and female patients as well as patients with and without high school diploma., Conclusions: The findings support the psychometric properties of the CHLT-30-Chinese for measuring cancer health literacy as a continuous trait and CHLT-6-Chinese for identifying patients with limited cancer health literacy with high precision. The two tools are recommended for use in both daily practice and clinical trials., (© 2021 John Wiley & Sons Australia, Ltd.)

Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients., Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3-5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment., Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65-93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs., Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest. All authors have nothing to disclose. All authors received no funding or sponsorship. No financial disclosure. There is no conflict of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: KPL has served as a consultant to Pfizer and Seattle Genetics. NMLB has received travel grants from Pfizer, Lilly, and Genomic Health; and reports speaker fees from Pfizer and AbbVie. All other authors declare no competing interests. The work was supported by the National Cancer Institute at the National Institute of Health (K99CA237744 awarded to KPL) and the Wilmot Research Fellowship Award (awarded to KPL).

Competing Interests: Declaration of Competing Interest Dr. Giri is supported in part by the Walter B. Frommeyer Fellowship in Investigative Medicine at the University of Alabama at Birmingham and reports receiving research funding from Carevive Systems and Pack Health and honoraria from Carevive Systems. Dr. Subbiah is supported by the Andrew Sabin Family Foundation Fellowship and the American Cancer Society (Clinician Scientist Development Grant).

The specialized cholesterol/sphingolipid-rich membrane domains termed lipid rafts are highly dynamic in the cancer cells, which rapidly assemble effector molecules to form a sorting platform essential for oncogenic signaling transduction in response to extra- or intracellular stimuli. Density-based membrane flotation, subcellular fractionation, cell surface biotinylation, and co-immunoprecipitation analyses of bichalcone analog ((E)-1-(4-Hydroxy-3-((4-(4-((E)-3-(pyridin-3-yl)acryloyl)phenyl)piperazin-1-yl)methyl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (TSWU-BR4)-treated cancer cells showed dissociation between GRP78 and p85α conferring the recruitment of PTEN to lipid raft membranes associated with p85α. Ectopic expression of GRP78 could overcome induction of lipid raft membrane-associated p85α-unphosphorylated PTEN complex formation and suppression of GRP78PI3KAktGTP-Rac1-mediated and GRP78-regulated PERKNrf2 antioxidant pathway and cancer cell invasion by TSWU-BR4. Using specific inducer, inhibitor, or short hairpin RNA for ASM demonstrated that induction of the lipid raft membrane localization and activation of ASM by TSWU-BR4 is responsible for perturbing homeostasis of cholesterol and ceramide levels in the lipid raft and ER membranes, leading to alteration of GRP78 membrane trafficking and subsequently inducing p85α-unphosphorylated PTEN complex formation, causing disruption of GRP78PI3KAktGTP-Rac1-mediated signal and ER membrane-associated GRP78-regulated oxidative stress balance, thus inhibiting cancer cell invasion. The involvement of the enrichment of ceramide to lipid raft membranes in inhibition of NF-κB-mediated MMP-2 expression was confirmed through attenuation of NF-κB activation using C2-ceramide, NF-κB specific inhibitors, ectopic expression of NF-κB p65, MMP-2 promoter-driven luciferase, and NF-κB-dependent reporter genes. In conclusion, localization of ASM in the lipid raft membranes by TSWU-BR4 is a key event for initiating formation of ceramide-enriched lipid raft membrane platforms, which causes delocalization of GRP78 from the lipid raft and ER membranes to the cytosol and formation of p85α-unphosphorylated PTEN complexes to attenuate the GRP78-regulated oxidative stress balance and GRP78p85αAktGTP-Rac1NF-κBMMP-2-mediated cancer cell invasion., Competing Interests: The authors declare no conflict of interest.

Palliative chemotherapy is increasingly used in cancer patients near end of life. With the development of newer anticancer agents which have less side effects and higher expected efficacy, the decision on palliative chemotherapy in patients near end of life is complex. This article illustrates how oncologist and palliative care physicians can work together effectively. This article also gives an overview about the risks of palliative chemotherapy near end of life, patients' and physicians' perspectives in choosing the aggressive treatment and describes what an oncologist should do when facing this challenging situation.

Background: Breathlessness is common in patients with advanced cancer. Using a multidisciplinary approach for relieving this challenging symptom was believed to be just a theory. The "SOB Program" was implemented in our institution in March 2013., Measures: An audit of medical records before and after implementation of the "SOB Program" was performed to identify any changes in practice after implementation, specifically in the use of nonpharmacologic interventions., Intervention: The "SOB Program" is a multidisciplinary service in our department, using both pharmacologic and nonpharmacologic interventions for all patients with advanced cancer who have dyspnea., Outcomes: There was a marked increase in the use of nonpharmacologic interventions after the "SOB Program" (26.86% preimplementation vs. 89.35% postimplementation). Patients joining the program also had satisfactory improvement in breathlessness., Conclusions/lessons Learned: A multidisciplinary approach for breathlessness control is both feasible and practical. Similar services can be promoted in other palliative care centers., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The association between use of oral bisphosphonates and cancer development in elderly women is still uncertain, and previous studies have shown controversial results. We used a nationwide, population-based database to explore the relationship between the use of alendronate, an oral bisphosphonate agent used for the treatment of osteoporosis, and the risk of all malignancies in women with osteoporosis and age over 55 years. In the study group, we included 6906 women with osteoporosis (age, mean ± SD, 73.4 ± 8.4 years) taking oral alendronate, who were selected from a 1,000,000 sample cohort dataset collected between January 1998 and December 2009. Another 20,697 age- and comorbidity-matched women (73.5 ± 8.4 years) without bisphosphonates treatment were included in the control group. No subjects had any history of being diagnosed with cancer before inclusion. We used a log-rank test to analyze the differences in accumulated cancer-free survival rates between these two groups. A Cox proportional-hazard model, adjusted for confounding factors, was used to evaluate the association between alendronate use and the development of all cancer events in postmenopausal women with osteoporosis. During the mean follow-up period of 4.8 years, 821 patients from the study group and 2646 patients from the control group had new cancers. There was no significant difference in cancer incidence between alendronate users and controls (11.9% versus 12.8%, p = 0.054). The person-year incidence of newly-developed cancer in alendronate users and controls was 28.0 and 29.4 per 1000 person-years, respectively. Alendronate use was not associated with increased risk of cancer development in women with osteoporosis (adjusted hazard ratio, 1.05; 95% confidence interval [CI], 0.97-1.13; p = 0.237). However, due to the limited study size and underpowered results, further larger prospective studies or meta-analysis are suggested to further confirm our findings., (Copyright © 2012 American Society for Bone and Mineral Research.)

Unlabelled: INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management., Methods: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images., Results: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions., Conclusions: (18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions., (© 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.)

The PI3K-AKT pathway and Aurora kinase play essential roles in such cellular processes as cell survival, angiogenesis, and differentiation, and are usually expressed at maximum levels during cancer cell proliferation. The present study investigated the effect of the natural compound, 16-hydroxycleroda-3,13-dien-15,16-olide (PL3), on regulating the PI3K-AKT pathway and Aurora B, which led to cancer cell apoptosis. PL3 acts as a PI3K inhibitor by influencing cell survival, signaling transduction, and cell cycle progression. It was observed that PL3 targeted and induced dephosphorylation of the PI3K pathway, degradation of Aurora B and mitotic-related gene expressions, and sequentially shut down the cell cycle. This eventually resulted in cell death. As Aurora B was downregulated, spindle dysfunction and destruction of the G₂/M phase checkpoint resulted in DNA-damaged cells undergoing apoptosis. Moreover, PL3 also resensitized T315I-mutated Bcr-ABL+ BA/F3 cells to improve the cytotoxicity of Imatinib in Imatinib-resistant cell line. Taken together, PL3 can perturb the PI3K-AKT pathway and Aurora B resulting in gene silencing and cell cycle disturbance. It was demonstrated that PL3 acted like a novel small-molecule PI3K modulator, thereby potentially contributing to cancer chemotherapy and combination medication., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Recently, concerns have been raised that angiotensin II receptor blockers (ARBs) may be associated with an increased risk for cancer development. However, the relation between ARBs and cancer is still unclear. Therefore, a nationwide population-based study was conducted to investigate the possible influence of ARBs on the occurrence of new cancers in patients with hypertension by using the Taiwan National Health Insurance database. A total of 109,002 patients with newly diagnosed hypertension were identified from a cohort database of 1 million individuals from January 1, 1998, to December 31, 2006. Among them, 40,124 (36.8%) had received ARBs for hypertension. The end point was the development of any type of cancer before the end of 2007. During an average of 5.7 ± 2.6 years of follow-up, a total of 9,067 cases of new cancer occurrence were observed. The log-rank test showed that the occurrence rate of newly diagnosed cancers in the subjects receiving ARBs was significantly lower than those receiving treatment without ARBs (ARBs vs controls 3,082 vs 5,985, p <0.001). After adjusting for age, gender, co-morbidities, and medications for hypertension control, ARB use was found to be independently associated with a decreased risk for cancer occurrence (hazard ratio 0.66, 95% confidence interval 0.63 to 0.68, p <0.001). In conclusion, long-term use of ARBs is associated with a lower incidence of cancer occurrence, thereby suggesting that ARBs may prevent cancer development., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Alternative splicing involves differential exon selection of a gene transcript to generate mRNA and protein isoforms with structural and functional diversity. Abnormal alternative splicing has been shown to be associated with malignant phenotypes of cancer cells, such as chemo-resistance and invasive activity. Screening small molecules and drugs for modulating RNA splicing in human hepatocellular carcinoma cell line Huh-7, we discovered that amiloride, distinct from four pH-affecting amiloride analogues, could "normalize" the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts. Our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF, and decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, and increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulates kinases and up-regulates phosphatases in the signal pathways known to affect splicing factor protein phosphorylation. These amiloride effects of "normalized" oncogenic RNA splicing and splicing factor hypo-phosphorylation were both abrogated by pre-treatment with a PP1 inhibitor. Global exon array of amiloride-treated Huh-7 cells detected splicing pattern changes involving 584 exons in 551 gene transcripts, many of which encode proteins playing key roles in ion transport, cellular matrix formation, cytoskeleton remodeling, and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. Other human solid tumor and leukemic cells, but not a few normal cells, showed similar amiloride-altered RNA splicing with devitalized consequence. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of RNA splicing for cancer therapeutics.

The aim of this study was to determine if attenuation correction (AC) in a dual-head, coincidence, positron emission tomography imaging system (Co-PET) improved image quality, lesion detection, patient staging and management of various malignant neoplasms, compared to non-attenuation corrected (NAC) images. Thirty patients with known or suspected malignant neoplasms underwent fluorodeoxyglucose (FDG) Co-PET, which was correlated with histopathology, computed tomography (CT) and other conventional imaging modalities and clinical follow-up. The number and location of FDG avid lesions detected on the AC images and NAC Co-PET images were blindly assessed by two independent observers. Semi-quantitative grading of image clarity and lesion-to-background quality was performed. This revealed markedly improved image clarity and lesion-to-background quality in the AC versus NAC Co-PET images. AC Co-PET was statistically superior to NAC Co-PET in relation to lesion detection (P<0.01) and tumour staging (P<0.01). NAC Co-PET demonstrated 51 of the 65 lesions (78%) detected by AC Co-PET. AC Co-PET altered tumour staging in five additional patients (16%) compared to NAC Co-PET. Management was altered in two of these five patients.