Trends in the medical repatriation of Filipino seafarers: a ten year study of a Philippine maritime shipping company (OSM Maritime).

BACKGROUND: Seafarers, confronted with unique health challenges, occasionally necessitate medical repatriation. This study examines the trends in medical repatriation cases among Filipino seafarers employed by OSM Maritime shipping company over a 10-year period from 2013 to 2022. MATERIALS AND METHODS: Medical records of OSM Maritime seafarers were reviewed, obtaining causes for and dates of medical repatriation. International Classification of Diseases (ICD-11) was utilised to classify repatriation cases. Proportion of repatriation cases were calculated and their annual trends were analysed. RESULTS: Our findings reveal that the majority of repatriation cases are attributed to injury/trauma (19.91%), musculoskeletal (18.40%), gastrointestinal (16.56%), cardiovascular (8.77%), infectious (6.82%), and genitourinary conditions (5.30%). Significantly, the study identifies a declining trend in the proportion of cardiovascular, gastrointestinal, and genitourinary conditions in annual repatriation cases, particularly in ischaemic heart conditions, cholelithiasis, cholecystitis, and urinary calculus. CONCLUSIONS: These results emphasize the critical need for multisectoral collaboration to enhance seafarers' health and well-being. Prioritizing comprehensive care programmes, ensuring safe working conditions, and exploring holistic healthcare initiatives are essential steps to enhance seafarers' occupational health.

Health risk classification patterns among Filipino seafarers. Analysis from a pre-employment clinic in the Philippines: a 5-year review.

BACKGROUND: Seafaring is a demanding profession that exposes individuals to unique health risks and challenges. This study investigates risk classification patterns among seafarers who underwent physical and medical examination at the Nordic Medical Clinic, a pre-employment clinic in the Philippines. MATERIALS AND METHODS: The analysis involved data obtained from medical records, including demographic information, diagnoses, medical risk classification, corresponding management, and occupational details. medical risk classification, based on guidelines from the Philippine Department of Labour and Employment, categorised fit to work seafarers into risk class A, B, or C. Descriptive statistics and statistical tests, with a significance level set at p < 0.05, were utilised for data analysis using R Studio (version 4.2.3). RESULTS: The study population consisted of 11,831 seafarers seen at the Nordic Medical Clinic between 2018 and 2022. The results revealed a significant proportion of seafarers falling into higher risk classifications, with risk class C being the most prevalent at 48.16%. Pre-employment medical examinations (PEME) to fit to work duration demonstrated a significant association with risk classification, revealing that lower-risk classes had shorter fit-to-work times compared to higher-risk classes. Moreover, risk classification exhibited uneven distribution across specific demographic and occupational characteristics, with older seafarers, males, married individuals, and those in higher-ranking positions having a higher proportion of risk class C. CONCLUSIONS: Our findings highlight the need for comprehensive and customised pre-boarding medical screening standards for seafarers based on factors such as their specific role, vessel type, voyage, contract length, and work location. Moreover, health implementation of health promotion and preventive strategies that are based on the specific occupational and demographic needs of the seafarers are needed.

Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery. Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months. Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons. Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission. Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

Neuropathic pain prevalence and risk factors in head and neck cancer survivors.

BACKGROUND: Neuropathic pain (NP) is a debilitating symptom among head and neck cancer (HNC) survivors although few large studies report its prevalence and associated risk factors. METHODS: A cross-sectional survey assessing demographic, behavioral, and clinical risk factors for NP. NP was assessed using the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS). RESULTS: Forty-five percent (227/505) reported having pain including 13.7% (69/505) who were positive for S-LANSS. Reported pain sites were in the regions of the head and oral cavity (46.2%) and neck and throat (41.5%). Despite a higher self-reported use of analgesic medication (NP+ = 41.2%; NP- = 27.4%; p = 0.020) and alternative pain therapies (NP+ = 19.1%; NP- = 8.4%; p = 0.009), severe pain was more prevalent among those with NP (N+ = 23.2%; NP- = 13.3%; p = 0.004). Adjusted for opioid medications, ethnicity/race, age, surgery, depression, and comorbidities were risk factors for NP. CONCLUSION: NP remains prevalent in HNC survivors highlighting the importance of routine pain surveillance.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

Circulating microRNAs as Biomarkers of Hepatic Fibrosis in Schistosomiasis Japonica Patients in the Philippines.

Host-derived microRNAs (miRNAs) play important regulatory roles in schistosomiasis-induced hepatic fibrosis. This study analyzed selected serum miRNAs among Filipino schistosomiasis japonica patients with ultrasound (US)-detectable hepatic fibrosis. A prospective cohort study design with convenience sampling was employed from 2017 to 2019. The study sites were eight endemic barangays in Leyte, Philippines. Eligible chronic schistosomiasis patients with varying severities of hepatic fibrosis were enrolled in the cohort and serially examined at 6, 12, and 24 months from baseline. Baseline serum miR-146a-5p, let-7a-5p, miR-150-5p, miR-122-5p, miR-93-5p, and miR200b-3p were measured using RT-qPCR. A total of 136 chronic schistosomiasis patients were included in this prospective cohort study. Approximately, 42.6% had no fibrosis, 22.8% had mild fibrosis, and 34.6% had severe fibrosis at baseline The serum levels of the antifibrotic miR-146a (p < 0.0001), miR-150 (p = 0.0058), and let-7a (p < 0.0001) were significantly lower in patients with hepatic fibrosis while the profibrotic miR-93 (p = 0.0024) was elevated. miR-146a-5p (AUC = 0.90, 95% CI [0.84, 0.96], p < 0.0001) has the most promising potential to differentiate patients with (n = 78) versus without (n = 58) hepatic fibrosis. The baseline level of serum miR-146-5p was significantly different in patients with progressive fibrosis (n = 17) compared to those who never developed fibrosis (n = 30, p < 0.01) or those who had fibrosis reversal (n = 20, p < 0.01) after 24 months. These findings demonstrate the potential utility of serum miRNAs, particularly of miR-146a, as a supplementary tool for assessing hepatic fibrosis in chronic schistosomiasis japonica patients.

Proton Beam Therapy for Esophageal Cancer.

Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at risk. In addition, the anatomic location of the esophagus raises challenges for radiotherapy due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These challenges propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. Several dosimetric studies support the potential advantages of PBT for esophageal cancer treatment however, translation of these results to improved clinical outcomes remains unclear with limited clinical data, especially in large populations. Studies on the effect on quality of life are likewise lacking. Here, we review the existing and emerging role of PBT for esophageal cancer, including treatment planning, early clinical comparisons of PBT with photon-based techniques, recently concluded and ongoing clinical trials, challenges and toxicities, effects on quality of life, and global inequities in the treatment of esophageal cancer.

Diagnostic Performance of Parasitological, Immunological, Molecular, and Ultrasonographic Tests in Diagnosing Intestinal Schistosomiasis in Fieldworkers From Endemic Municipalities in the Philippines.

Schistosomiasis remains to ha/ve a significant public health impact in the Philippines. The Kato-Katz (K-K) technique is the reference standard and most used technique for definitive diagnosis of intestinal schistosomiasis for control programs in endemic regions. However, this has a very low sensitivity when applied in areas of low endemicity and patients with light infection. Hence, this study determined the diagnostic performance of immunological, molecular, parasitological, and ultrasonographic tests in diagnosing intestinal schistosomiasis in endemic municipalities in the Philippines. We performed a community-based cross-sectional study to determine the positivity of schistosomiasis in Leyte, Philippines. The diagnostic performance of five different detection techniques: (1) three stool K-K with duplicate smears; (2) soluble egg antigen IgG ELISA; (3) urine point-of-care circulating cathodic antigen (POC-CCA) test; (4) detection of Schistosoma japonicum circulating DNA (SjcDNA) in serum and urine samples; (5) focused abdominal ultrasound (US), were also obtained in this study. Multiple stool examinations enhanced the sensitivity of K-K from 26.2% (95% CI [16.4, 38.8]) with single stool to 53.8% (95% CI [41.1, 66.1]) and 69.2% (95% CI [56.4, 80.0]) with two and three stools from consecutive days, respectively. Among the SjcDNA nucleic acid amplification test (NAAT)-based detection assays, loop-mediated isothermal amplification (LAMP) PCR using sera had the highest sensitivity at 92.3% (95% CI [82.2, 97.1]) with LAMP consistently identifying more positive cases in both serum and urine samples. This study showed that single stool K-K, which remains the only diagnostic test available in most endemic areas in the Philippines, had low sensitivity and failed to identify most patients with light infection. SjcDNA detection assay and POC-CCA urine test were more sensitive than stool microscopy in detecting schistosomiasis. On the other hand, US was less sensitive than the widely utilized K-K technique in diagnosing schistosomiasis. This study emphasizes the need to revisit the use of single stool K-K in the surveillance and case detection of schistosomiasis in endemic areas of the Philippines. The availability of advanced and more sensitive diagnostic tests will help better control, prevent, and eliminate schistosomiasis in the country.

Predictors of mortality among inpatients with COVID-19 infection in a tertiary referral center in the Philippines.

Objectives: The aim of this study was to determine the predictors of mortality and describe laboratory trends among adults with confirmed COVID-19. Methods: The medical records of adult patients admitted to a referral hospital with COVID-19 were retrospectively reviewed. Demographic and clinical characteristics, and laboratory parameters, were compared between survivors and non-survivors. Predictors of mortality were determined by multivariate analysis. Mean laboratory values were plotted across illness duration. Results: Of 1215 patients, 203 (16.7%) had mild, 488 (40.2%) moderate, 183 (15.1%) severe, and 341 (28.1%) critical COVID-19 on admission. In-hospital mortality was 18.2% (0% mild, 6.1% moderate, 15.8% severe, 47.5% critical). Predictors of mortality were age ≥ 60 years, COPD, qSOFA score ≥ 2, WBC > 10 × 109/L, absolute lymphocyte count < 1000, neutrophil ≥ 70%, PaO2/FiO2 ratio ≤ 200, eGFR < 90 mL/min/1.73 m2, LDH > 600 U/L, and CRP > 12 mg/L. Non-survivors exhibited an increase in LDH and decreases in PaO2/FiO2 ratio and eGFR during the 2nd-3rd week of illness. Conclusion: The overall mortality rate was high. Predictors of mortality were similar to those of other reports globally. Marked inflammation and worsening pulmonary and renal function were evident among non-survivors by the 2nd-3rd week of illness.

The molecular heterogeneity of the precancerous breast affects drug efficacy.

In the therapeutic domain, targeted therapies have been shown to be generally more effective when given to patients with tumors that harbor the targeted aberration. This principle has not been tested in cancer prevention despite evidence that molecular heterogeneity accompanies the multi-step progression to invasive disease. We hypothesized that efficacy of agents targeting the precancerous state varies based on timing of the treatment relative to the underlying molecular changes. MCF10A cell line-based model of the multi-step progression to TNBC was used. Global proteomic patterns were obtained and growth-inhibitory effects of selected agents were correlated with the underlying molecular stage of progression. These analyses revealed that most protein alterations were acquired in the normal-to-atypia (preneoplasia) transition, with only handful aberrations acquired hereafter. The efficacy of small molecule inhibitors of the AKT/MEK pathway was associated with the underlying pathway levels. Similarly, fluvastatin was more effective in inhibiting cell proliferation earlier in the progression model. However, the nonspecific inhibitors, aspirin and metformin, were equally ineffective in inhibiting proliferation across the progression model. Our data provides proof-of-principle that in the prevention domain, treatment with agents developed to target specific pathways, will need to consider the molecular heterogeneity of the precancerous breast in order to achieve maximum efficacy.

Clinical characteristics of patients with asymptomatic and symptomatic COVID-19 admitted to a tertiary referral centre in the Philippines.

Objectives: To describe the clinical profile and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) across the spectrum of disease severity. Methods: This retrospective study included adult patients with confirmed COVID-19 infection admitted to a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease severity categories. Results: Of 1500 patients with COVID-19, 14.8% were asymptomatic, 13.5% had mild disease, 36.6% had moderate disease, 12.3% had severe disease and 22.7% had critical disease. Asymptomatic patients were admitted for a concurrent condition or for isolation. Patients aged >60 years, male gender and with co-morbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastrointestinal symptoms and decreased sensorium were more common in patients with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. The overall mortality rate was 15.1%. Adopting a symptom-based strategy reduced the length of hospitalization from a median of 13 [interquartile range (IQR) 7-21] days to 9 (IQR 5-14) days. Conclusion: The clinical profile and outcomes for this cohort of patients with COVID-19 was consistent with published reports. Asymptomatic infection was common, and universal testing may be a valuable strategy in the correct context, given the implications for infection control. A symptom-based strategy was found to reduce the length of hospitalization considerably.

Bibliometric analysis of schistosomiasis research in Southeast Asia (1908-2020).

OBJECTIVES: This study determined the characteristics and trends of published articles regarding schistosomiasis in Southeast Asian countries through a bibliometric analysis. METHODS: Using the Scopus database, we identified all original research articles on schistosomiasis from 1908 to 2020 from SEA countries: Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam. Bibliographic and citation information was obtained, and visualization of collaboration networks of countries and keywords related to schistosomiasis was conducted using VOSviewer software. RESULTS: We obtained 528 schistosomiasis articles published between 1908 and 2020 from SEA countries. The number of publications continued to increase and peaked from 2000 until 2020. The Philippines had the highest number of publications (n = 231), followed by Thailand (n = 153), and Malaysia (n = 64). The leading journals with the highest number of publications in this field include the Southeast Asian Journal of Tropical Medicine and Public Health (n = 96), Acta Tropica (n = 27), and Plos Neglected Tropical Diseases (n = 24). The most common keywords related to schistosomiasis research in SEA were "schistosomiasis", "Schistosoma japonicum", "Schistosoma mekongi", "Schistosoma mansoni", and "praziquantel". International collaboration was significantly correlated with scientific productivity for schistosomiasis research. CONCLUSION: Our study showed the research landscape, trends and development, and collaboration among researchers in schistosomiasis in SEA. Our results also revealed the limited schistosomiasis research in several SEA countries. There is a need for more research to improve our understanding of the epidemiology of schistosomiasis in SEA, which can help in improving the control and prevention of this disease.

Variations in pain prevalence, severity, and analgesic use by duration of survivorship: a cross-sectional study of 505 post-treatment head and neck cancer survivors.

BACKGROUND: Studies suggest a high prevalence of pain in head and neck cancer (HNC) patients at diagnosis, during and after treatment; however, these studies had small sample sizes and did not comprehensively assess factors known to influence pain. We surveyed a large cohort of HNC survivors to determine variations in the prevalence of pain, its treatment and management by duration of survivorship, and assessed a comprehensive list of risk factors. METHODS: A cross sectional survey of post-treatment survivors of HNC during routine follow-up clinic visits. RESULTS: A total of 505 HNC survivors with a median follow up of 3 years from cancer diagnosis were included in the study. Overall, 45% (n = 224) reported pain and 14.5, 22 and 7% reported use of prescribed pain medication, over-the-counter pain medication and alternative pain therapies, respectively. Prevalence of severe pain was 7.3% and did not vary significantly by years of survivorship (< 1 year = 5.7%; 1 to < 3 years = 7.1%; 3 to < 8 years = 7.6%; 8 years or more =9.7%; P = 0.392). However, use of prescribed pain medication significantly varied by years of survivorship (< 1 year = 45.7%; 1 to < 3 years = 24.6%; 3 to < 8 years = 18.9; 8 years or more = 18.3%; p < 0.001). Of note, a significant proportion of survivors reported moderate to severe pain (moderate to severe = 55.7% versus none to mild = 44.3%) despite step 3 analgesic use (p < 0.001). Multivariable regression shows that recurrent disease (OR 6.77, 95% CI [1.44, 31.80]), history of chemotherapy (OR 6.00, 95% CI [2.10, 17.14]), and depression (Mild-moderate OR 5.30, 95% CI [2.20, 12.78]; Major OR 8.00, 95% CI [2.67, 23.96]) were significant risk factors for severe pain. CONCLUSIONS: We identified a high prevalence of pain among HNC survivors and determined that analgesic use varied by the duration of survivorship. Therefore, routine surveillance for pain must be consistent throughout the course of survivorship.

Association of mycoplasma with prostate cancer: A systematic review and meta-analysis.

Mycoplasmas are emerging sexually transmitted pathogens usually associated with male urinary tract infection, non-gonococcal urethritis (NGU), infertility, and prostate cancer. In this study, we review the evidence linking mycoplasma infection and prostate cancer. We conducted a systematic review and meta-analysis based on PRISMA guidelines. Four electronic databases were reviewed through January 31, 2021. Studies were eligible for inclusion if odds ratio for prevalence or incidence of colonization and/or infection were provided or calculable. All included studies were evaluated independently by three reviewers. The quality of the included studies was assessed using the Newcastle-Ottawa Scale for Case-Control Studies. Statistical analysis was done using Review Manager Version 5.4. A total of 183/744 (24.6 %) patients with prostate cancer compared to 87/495 (17.58 %) patients with benign prostatic hyperplasia (BPH) tested positive for Mycoplasma spp., while 86/666 (12.91 %) and 11/388 (2.84 %) prostate cancer patients and BPH patients, respectively, had Ureaplasma spp. infections. This meta-analysis showed that prostate cancer patients had 2.24 times higher odds (p = 0.0005) of being colonized with any species of Mycoplasma spp. and 3.6 times increased odds (p = 0.008) of being colonized with any species of Ureaplasma spp. In conclusion, patients with prostate cancer were more likely to be colonized with Mycoplasma spp. or Ureaplasma spp. compared to patients with BPH, which highlights the potential association between chronic infection and cancer. However, more studies are needed to determine the specific role that mycoplasma plays in the pathogenesis of prostate cancer.

Efficacy of fluvastatin and aspirin for prevention of hormonally insensitive breast cancer.

PURPOSE: Primary prevention of hormonally insensitive breast cancers remains an important clinical need and repurposing existing low-toxicity drugs represents a low-cost, efficient strategy for meeting this goal. This study targeted the cholesterol pathway using fluvastatin, a cholesterol-lowering drug, and aspirin, an AMPK activator that acts as a brake in the cholesterol pathway, in a transgenic mouse model of triple-negative breast cancer (TNBC). METHODS: Using SV40C3 TAg mice, the efficacy and mechanism of fluvastatin, aspirin, or both in combination were compared with vehicle alone. RESULTS: Sixteen-weeks of fluvastatin treatment resulted in significant delay in onset of tumors (20 weeks vs. 16.8 weeks in vehicle treatment, p = 0.01) and inhibited tumor incidence and tumor multiplicity by 50% relative to the vehicle control. In animals that developed tumors, fluvastatin treatment inhibited tumor weight by 75% relative to vehicle control. Aspirin alone did not significantly affect tumor latency, tumor incidence or tumor burden compared to vehicle control. Fluvastatin and aspirin in combination delayed the onset of tumors but failed to inhibit tumor incidence and tumor multiplicity. The growth-inhibitory effects of fluvastatin were mediated through increased FAS/FASL mediated apoptotic cell death that was characterized by increased cleaved PARP and driven in part by depletion of an isoprenoid, geranyl geranyl pyrophosphate (GGPP). CONCLUSIONS: In line with NCI's emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.

Combinatorial effect of radium-223 and irreversible electroporation on prostate cancer bone metastasis in mice.

BACKGROUND: Metastatic prostate cancer in bone is difficult to treat as the tumor cells are relatively resistant to hormonal or chemotherapies when compared to primary prostate cancer. Irreversible electroporation (IRE) is a minimally invasive ablation procedure that has potential applications in the management of prostate cancer in bone. However, a common limitation of IRE is tumor recurrence, which arises from incomplete ablation that allows remaining cancer cells to proliferate. In this study, we combined IRE with radium-223 (Ra-223), a bone-seeking radionuclide that emits short track length alpha particles and thus is associated with reduced damage to the bone marrow and evaluated the impact of the combination treatment on bone-forming prostate cancer tumors. METHODS: The antitumor activity of IRE and Ra-223 as single agents and in combination was tested in vitro against three bone morphogenetic protein 4 (BMP4)-expressing prostate cancer cell lines (C4-2B-BMP4, Myc-CaP-BMP4, and TRAMP-C2-BMP4). Similar evaluation was performed in vivo using a bone-forming C4-2B-BMP4 tumor model in nude mice. RESULTS: IRE and Ra-223 as monotherapy inhibited prostate cancer cell proliferation in vitro, and their combination resulted in significant reduction in cell viability compared to monotherapy. In vivo evaluation revealed that IRE with single-dose administration of Ra-233, compared to IRE alone, reduced the rate of tumor recurrence by 40% following initial apparent complete ablation and decreased the rate of proliferation of incompletely ablated tumor as quantified in Ki-67 staining (53.58 ± 16.0% for IRE vs. 20.12 ± 1.63%; for IRE plus Ra-223; p = 0.004). Histological analysis qualitatively showed the enhanced killing of tumor cells adjacent to bone by Ra-223 compared to those treated with IRE alone. CONCLUSION: IRE in combination with Ra-223, which enhanced the destruction of cancer cells that are adjacent to bone, resulted in reduction of tumor recurrence through improved clearance of proliferative cells in the tumor region.

Recent Advances in Nanomedicine for the Diagnosis and Treatment of Prostate Cancer Bone Metastasis.

Patients with advanced prostate cancer can develop painful and debilitating bone metastases. Currently available interventions for prostate cancer bone metastases, including chemotherapy, bisphosphonates, and radiopharmaceuticals, are only palliative. They can relieve pain, reduce complications (e.g., bone fractures), and improve quality of life, but they do not significantly improve survival times. Therefore, additional strategies to enhance the diagnosis and treatment of prostate cancer bone metastases are needed. Nanotechnology is a versatile platform that has been used to increase the specificity and therapeutic efficacy of various treatments for prostate cancer bone metastases. In this review, we summarize preclinical research that utilizes nanotechnology to develop novel diagnostic imaging tools, translational models, and therapies to combat prostate cancer bone metastases.

Radiopaque scaffolds based on electrospun iodixanol/polycaprolactone fibrous composites.

Grafts based on biodegradable polymer scaffolds are increasingly used in tissue-engineering applications as they facilitate natural tissue regeneration. However, monitoring the position and integrity of these scaffolds over time is challenging due to radiolucency. In this study, we used an electrospinning method to fabricate biodegradable scaffolds based on polycaprolactone (PCL) and iodixanol, a clinical contrast agent. Scaffolds were implanted subcutaneously into C57BL/6 mice and monitored in vivo using longitudinal X-ray imaging and micro-computed tomography (CT). The addition of iodixanol altered the physicochemical properties of the PCL scaffold; notably, as the iodixanol concentration increased, the fiber diameter decreased. Radiopacity was achieved with corresponding signal enhancement as iodine concentration increased while exhibiting a steady time-dependent decrease of 0.96% per day in vivo. The electrospun scaffolds had similar performance with tissue culture-treated polystyrene in supporting the attachment, viability, and proliferation of human mesenchymal stem cells. Furthermore, implanted PCL-I scaffolds had more intense acute inflammatory infiltrate and thicker layers of maturing fibrous tissue. In conclusion, we developed radiopaque, biodegradable, biocompatible scaffolds whose position and integrity can be monitored noninvasively. The successful development of other imaging enhancers may further expand the use of biodegradable scaffolds in tissue engineering applications.

Fully automated preparation of 68Ga-PSMA-11 at curie level quantity using cyclotron-produced 68Ga for clinical applications.

68Ga-PSMA-11 is currently one of the most investigated PET agents for imaging both recurrent prostate cancer and relevant metastases; however, the production and distribution of 68Ga-PSMA-11 is limited to a supply of only a few daily doses when using a commercially available 68Ge/68Ga generator. 68Ge/68Ga generators deliver only a modest amount of activity, up to 1850 MBq (50 mCi), when new, but it decreases with time. Additionally, the production of 68Ga/68Ge generators has not been able to meet the increasing demand of 68Ga radiotracers. In response to the need for a more economically viable alternative, the focus of this study was to provide a simple and efficient method for producing 68Ga-PSMA-11, using cyclotron-produced 68Ga that is ready for routine clinical practice.