The Effect of Exercise on Reducing Lymphedema Severity in Breast Cancer Survivors.

Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is still under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases: PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded that daily, or nearly daily, exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

Survival outcomes and predicting intracranial metastasis in stage III non-small cell lung cancer treated with definitive chemoradiation: Real-world data from a tertiary cancer center.

PURPOSE/OBJECTIVE: Around 30% of patients with non-small cell lung cancers (NSCLC) are diagnosed with stage III disease at presentation, of which about 50% are treated with definitive chemoradiation (CRT). Around 65-80% of patients will eventually develop intracranial metastases (IM), though associated risk factors are not clearly described. We report survival outcomes and risk factors for development of IM in a cohort of patients with stage III NSCLC treated with CRT at a tertiary cancer center. MATERIALS/METHODS: We identified 195 patients with stage III NSCLC treated with CRT from January 2010 to May 2021. Multivariable logistic regression was used to generate odds ratios for covariates associated with development of IM. Kaplan-Meier analysis with the Log Rank test was used for unadjusted time-to-event analyses. P-value for statistical significance was set at < 0.05 with a two-sided test. RESULTS: Out of 195 patients, 108 (55.4%) had stage IIIA disease and 103 (52.8%) had adenocarcinoma histology. The median age and follow-up (in months) was 67 (IQR 60-74) and 21 (IQR 12-43), respectively. The dose of radiation was 60 Gy in 30 fractions for148 patients (75.9%). Of the 77 patients who received treatment since immunotherapy was available and standard at our cancer center, 45 (58.4%) received at least one cycle. During follow-up, 84 patients (43.1%) developed any metastasis, and 33 (16.9%) developed IM (either alone or with extracranial metastasis). 150 patients (76.9%) experienced a treatment delay (interval between diagnosis and treatment > 4 weeks). Factors associated with developing any metastasis included higher overall stage at diagnosis (p = 0.013) and higher prescribed dose (p = 0.022). Factors associated with developing IM included higher ratio of involved over sampled lymph nodes (p = 0.001) and receipt of pre-CRT systemic or radiotherapy for any reason (p = 0.034). On multivariate logistical regression, treatment delay (OR 3.9, p = 0.036) and overall stage at diagnosis (IIIA vs. IIIB/IIIC) (OR 2.8, p = 0.02) predicted development of IM. These findings were sustained on sensitivity analysis using different delay intervals. Median OS was not reached for the overall cohort, and was 43.1 months for patients with IM and 40.3 months in those with extracranial-only metastasis (p = 0.968). In patients with any metastasis, median OS was longer (p = 0.003) for those who experienced a treatment delay (48.4 months) compared to those that did not (12.2 months), likely due to expedited diagnosis and treatment in patients with a higher symptom burden secondary to more advanced disease. CONCLUSIONS: In patients with stage III NSCLC treated with definitive CRT, the risk of IM appears to increase with overall stage at diagnosis and, importantly, may be associated with experiencing a treatment delay (> 4 weeks). Metastatic disease of any kind remains the primary life-limiting prognostic factor in these patients with advanced lung cancer. In patients with metastatic disease, treatment delay was associated with better survival. Patients who experience a treatment delay and those initially diagnosed at a more advanced overall stage may warrant more frequent surveillance for early diagnosis and treatment of IM. Healthcare system stakeholders should strive to mitigate treatment delay in patients with locally NSCLC to reduce the risk of IM. Further research is needed to better understand factors associated with survival, treatment delay, and the development of IM after CRT in the immunotherapy era.

Emerging PET Tracers in Cardiac Molecular Imaging.

18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.

Investigating Cutaneous Squamous Cell Carcinoma in vitro and in vivo: Novel 3D Tools and Animal Models.

Cutaneous Squamous Cell Carcinoma (cSCC) represents the second most common type of skin cancer, which incidence is continuously increasing worldwide. Given its high frequency, cSCC represents a major public health problem. Therefore, to provide the best patients' care, it is necessary having a detailed understanding of the molecular processes underlying cSCC development, progression, and invasion. Extensive efforts have been made in developing new models allowing to study the molecular pathogenesis of solid tumors, including cSCC tumors. Traditionally, in vitro studies were performed with cells grown in a two-dimensional context, which, however, does not represent the complexity of tumor in vivo. In the recent years, new in vitro models have been developed aiming to mimic the three-dimensionality (3D) of the tumor, allowing the evaluation of tumor cell-cell and tumor-microenvironment interaction in an in vivo-like setting. These models include spheroids, organotypic cultures, skin reconstructs and organoids. Although 3D models demonstrate high potential to enhance the overall knowledge in cancer research, they lack systemic components which may be solved only by using animal models. Zebrafish is emerging as an alternative xenotransplant model in cancer research, offering a high-throughput approach for drug screening and real-time in vivo imaging to study cell invasion. Moreover, several categories of mouse models were developed for pre-clinical purpose, including xeno- and syngeneic transplantation models, autochthonous models of chemically or UV-induced skin squamous carcinogenesis, and genetically engineered mouse models (GEMMs) of cSCC. These models have been instrumental in examining the molecular mechanisms of cSCC and drug response in an in vivo setting. The present review proposes an overview of in vitro, particularly 3D, and in vivo models and their application in cutaneous SCC research.

Lifetime caffeine intake and the risk of epithelial ovarian cancer.

BACKGROUND: Caffeine intake has been inconsistently associated with the risk of ovarian cancer in previous studies. The measure of caffeine in these studies has not always distinguished between caffeinated and decaffeinated sources, and the time for which intake was assessed was often for late adulthood and thus may have excluded the etiologic window. We investigated lifetime caffeine intake from caffeinated coffee, black tea, green tea and cola sodas in relation to ovarian cancer risk. METHODS: Among 497 cases and 904 controls in a population-based case-control study in Montreal, Canada, lifetime intake of caffeinated coffee, black tea, green tea and cola sodas was assessed and used to calculate lifetime total intake of caffeine. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between caffeine intake and ovarian cancer risk overall, as well as by menopausal status. Multivariable polytomous logistic regression was used to estimate the associations for invasive and borderline ovarian cancers separately. RESULTS: Almost all participants (98.4% of cases and 97.5% of controls) had consumed caffeine in their lifetime. The mean (standard deviation) daily consumption of caffeine over the lifetime was of 117 (89) mg/day among cases and 120 (118) mg/day among controls. The OR (95% CI) of ovarian cancer for the highest versus lowest quartile of lifetime caffeine intake was 1.17 (0.83-1.64). According to menopausal status, the OR (95% CI) was 1.56 (0.85-2.86) for premenopausal women and 0.94 (0.66-1.34) for postmenopausal women, comparing the highest to lowest tertiles of intake. Associations for invasive and borderline ovarian cancers separately were similar to that observed for ovarian cancer overall. CONCLUSION: Lifetime caffeine intake was not strongly associated with ovarian cancer risk. A difference in relationship by menopausal status is possible.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: urethral histology.

The National Institutes of Health leveled new focus on sex as a biological variable with the goal of understanding sex-specific differences in health and physiology. We previously published a functional assessment of the impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology (Ruetten H, Wegner KA, Zhang HL, Wang P, Sandhu J, Sandhu S, Mueller B, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM. Am J Physiol Renal Physiol 317: F996-F1009, 2019). Here, we measured and compared five characteristics of urethral histology (urethral lumen diameter and area, epithelial cell count, epithelial and rhabdosphincter thickness, epithelial cell area, and total urethral area) in male and female 9-wk-old C57BL/6J mice using hematoxylin and eosin staining. We also compared male mice with castrated male mice, male and female mice treated with the steroid 5α-reductase inhibitor finasteride or testosterone, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that reduce prostate lobe mass. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed urethral histology, but none feminized male urethral histology (increased urethral epithelial area). Exogenous testosterone caused increased epithelial cell count in intact females but did not masculinize female urethral histology (decrease epithelial area). Our results lay a critical foundation for future studies as we begin to parse out the influence of hormones and cellular morphology on male and female urinary function.

Insight and Resources From a Study of the "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology.

The purpose of this symposium report is to summarize information from a session 3 oral presentation at the Society of Toxicologic Pathology Annual Symposium in Raleigh, North Carolina. Mice are genetically tractable and are likely to play an important role in elucidating environmental, genetic, and aging-related mechanisms of urinary dysfunction in men. We and others have made significant strides in developing quantitative methods for assessing mouse urinary function and our collaborators recently showed that aging male mice, like men, develop urinary dysfunction. Yet, it remains unclear how mouse prostate anatomy and histology relate to urinary function. The purpose of this report is to share foundational resources for evaluating mouse prostate histology and urinary physiology from our recent publication "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology: Functional Assessment." We will begin with a review of prostatic embryology in men and mice, then move to comparative histology resources, and conclude with quantitative measures of rodent urinary physiology.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment.

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter "baseline" of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

Clinical utility of daylight photodynamic therapy in the treatment of actinic keratosis - a review of the literature.

Actinic keratosis (AK) is an early in situ squamous cell carcinoma that results from UV light exposure and has the potential to evolve into invasive tumor. Therefore, it is crucial that AKs are monitored and treated appropriately. Photodynamic therapy (PDT) is a treatment option that is minimally invasive and leaves patients with cosmetically superior results. However, disadvantages of PDT include pain and lengthy clinic visits. Accordingly, there has been much interest in the use of daylight photodynamic therapy (daylight-PDT) as a more convenient and less painful alternative to conventional photodynamic therapy (c-PDT). Current evidence shows that daylight-PDT is noninferior to c-PDT in the short and long term. Patients reported decreased pain with daylight-PDT and were more satisfied with the procedure (P<0.001). Current evidence suggests that 2 hrs of daylight exposure was sufficient for treatment, and its efficacy does not appear to be limited by weather conditions. Given the decreased intensity of treatment, daylight-PDT is better for mild disease, as it is less effective in moderate-to-thick AKs. Though further studies are still needed to refine the technique, daylight-PDT is a potential alternative to c-PDT for thin-to-moderate AKs and should be offered to patients with lower pain tolerance or busy schedules.

Neutrophil depletion inhibits early and late monocyte/macrophage increase in lung inflammation.

Monocytes/macrophages have critical impact on outcomes of lung inflammation. Kinetics and mechanisms for the increase of monocytes/macrophages in lungs are not completely understood. To better understand these mechanisms, E. coli-LPS (250 micro grams; N = 35) or endotoxin-free saline (N = 5) were instilled intratracheally in Sprague-Dawley rats and the increase in monocytes/macrophages, neutrophils and monocyte chemotactic protein-1 (MCP-1) was quantified at various time points after LPS treatment. In contrast to typical pattern of neutrophil influx between 6 and 24 hours, monocytes/macrophages increased in two distinct phases, very early at 3 hours and late at 24 hours. The role of neutrophils in monocyte/macrophage increase was addressed in LPS-challenged neutropenic rats (N = 8). Neutrophil depletion before instillation of LPS abrogated the early as well as late monocyte/macrophage increases in the lung. Quantification of MCP-1, which is one of the major chemoattractants for monocytes, in lung homogenates showed similar concentrations in neutropenic and non-neutropenic LPS-challenged rats. These findings show that increase in monocytes/macrophages in lung occurs in two, early and late phases, both being dependent on neutrophils but not on MCP-1.