Institute Of Cancer Research Research Articles

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial

SummaryBackgroundTreatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia.MethodsThis was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres). Patients were aged 25–65 years with de-novo BCR-ABL1-negative acute lymphoblastic leukaemia. Patients with de-novo BCR-ABL1-positive acute lymphoblastic leukaemia were eligible if they were aged 19–65 years. Participants were randomly assigned (1:1) to standard-of-care induction therapy or standard-of-care induction therapy plus four doses of intravenous rituximab (375 mg/m2 on days 3, 10, 17, and 24). Randomisation used minimisation and was stratified by sex, age, and white blood cell count. No masking was used for patients, clinicians, or staff (including the trial statistician), although the central laboratory analysing minimal residual disease and CD20 was masked to treatment allocation. The primary endpoint was event-free survival in the intention-to-treat population. Safety was assessed in all participants who started trial treatment. This study is registered with ClincialTrials.gov, NCT01085617.FindingsBetween April 19, 2012, and July 10, 2017, 586 patients were randomly assigned to standard of care (n=292) or standard of care plus rituximab (n=294). Nine patients were excluded from the final analysis due to misdiagnosis (standard of care n=4, standard of care plus rituximab n=5). In the standard-of-care group, median age was 45 years (IQR 22–65), 159 (55%) of 292 participants were male, 128 (44%) were female, one (<1%) was intersex, and 143 (59%) of 244 participants had high-risk cytogenetics. In the standard-of-care plus rituximab group, median age was 46 years (IQR 23–65), 159 (55%) of 294 participants were male, 130 (45%) were female, and 140 (60%) of 235 participants had high-risk cytogenetics. After a median follow-up of 53·7 months (IQR 40·3–70·4), 3-year event-free survival was 43·7% (95% CI 37·8–49·5) for standard of care versus 51·4% (45·4–57·1) for standard of care plus rituximab (hazard ratio [HR] 0·85 [95% CI 0·69–1·06]; p=0·14). The most common adverse events were infections and cytopenias, with no difference between the groups in the rates of adverse events. There were 11 (4%) fatal (grade 5) events in induction phases 1 and 2 in the standard-of-care group and 13 (5%) events in the standard-of-care plus rituximab group). 3-year non-relapse mortality was 23·7% (95% CI 19·0–29·4) in the standard-of-care group versus 20·6% (16·2–25·9) in the standard-of-care plus rituximab group (HR 0·88 [95% CI 0·62–1·26]; p=0·49).InterpretationStandard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient.FundingCancer Research UK and Blood Cancer UK.

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway.

Fasudil is reported to be effective at protecting against ischaemic diseases, and at augmenting axon growth. In this study, we aim to evaluate its efficacy in promoting flap survival and reinnervation. Ninety-two Institute of Cancer Research (ICR) mice were used and divided into the control, Fasudil, LY294002, Fasudil+LY294002 groups, receiving a daily intraperitoneal injection of normal saline, Fasudil (10mg/kg), LY294002 (5mg/kg), and Fasudil (10mg/kg) + LY294002 (5mg/kg), respectively. On days 0 and 5, the blood perfusion and diameter of the iliolumbar artery in the pedicle of the flaps in the four groups were evaluated using laser speckling contrast imaging (LSCI). On day 5, the flaps were photographed and the necrosis rate of the flaps was calculated using Photoshop CS6. In addition, tissues were harvested from the flaps and divided into two parts. One part underwent routine cryosection and immunofluorescent staining using the antibody against CD31 for evaluation of the microvascular density in the four groups. In the other part, the expression of RhoA, ROCK1+2, p-CPI-17, p-MYPT, p-PTEN, p-PI3K, p-Akt, and vascular endothelial growth factor (VEGF) within the flaps were determined using western blotting. Moreover, at days 0, 7, 15, and 30 after flap surgery, the axons within the flaps were evaluated using immunofluorescent staining with the antibody against Neurofilament-200. It turned out that the necrosis rate was (24.4 ± 7.7)%, (5.2 ± 1.6)%, (29.8 ± 4.2)%, and (30.9 ± 7.1)%, respectively, in the control, Fasudil, LY294002, LY294002+Fasudil groups. There was a significant reduction in the necrosis rate of the flaps in the Fasudil group (P < .001). The LSCI and immunofluorescent staining demonstrated that Fasudil could significantly expand the diameter of the iliolumbar artery in the pedicle, boost the overall blood perfusion, and increase the microvascular density of the flaps in the Fasudil group (P < .05), which could all be abolished by PI3K inhibitor LY294002. On day 5, the expression of p-CPI-17, p-MYPT, and p-PTEN were downregulated, whereas pPI3K, p-Akt, and VEGF were upregulated in the Fasudil group (P < .001). As for reinnervation, Neurofilament-200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.

Awareness of Cervical Cancer among Staff Nurses in a Tertiary Level Cancer Centre in Bangladesh

Background: Cervical cancer is the second leading malignancy and cause of death in Bangladeshi women. Health professional’s misconceptions about the disease and lack of knowledge may worsen the situation. Nurses form a large proportion of the health care provider workforce. Among them who had opportunity to work in cancer hospital should know better about cervical cancer than other hospitals in the country. This survey was undertaken with an intention to address this important health issue by determining the awareness of cervical cancer among nurses at a tertiary cancer centre of Bangladesh.&#x0D; Objective: To provide the baseline information about the knowledge of cervical cancer and explore attitude and practice of cervical cancer screening among staff nurses.&#x0D; Methods: A pretested structured self-administered questionnaire based cross sectional survey was done on 154 staff nurses working in National Institute of Cancer Research and Hospital (NICRH), Dhaka, containing mostly recognition and some recall type questions about knowledge of cervical cancer, its risk factors, screening techniques, attitude towards cervical cancer screening and its practices.&#x0D; Results: 100% respondents heard the name of cervical cancer but 35.7% did not know about any of its risk factors and only 3.2% aware about more than 3 risk factors. Twenty seven percent not aware about any symptom, only 51.9% identified the foul smelling excessive vaginal discharge and irregular abnormal vaginal bleeding as the symptom and 16.8% know that post coital bleeding may be the symptom. Only 42.2% know VIA as a screening test, 39.6% know actual screening interval, 23.37% know who should be screened, 42.2% aware about HPV vaccine, 35.7% can do VIA, 42.2% said that they referred patient for screening but only 16.2% of themselves have ever been screened.&#x0D; Conclusion: The majority of nursing staff in NICRH had inadequate knowledge about cervical cancer screening and their attitude and practice towards cervical cancer screening could not be termed positive. There is an urgent need for orientation course for working nurses and integration of cervical cancer prevention issues in the existing curriculum of nurses in Bangladesh.&#x0D; Bangladesh J Obstet Gynaecol, 2020; Vol. 35(2): 102-106

Curcumin Suppresses Lead-Induced Inflammation and Memory Loss in Mouse Model and In Silico Molecular Docking.

This study examined the efficacy of curcumin (Cur) against lead (Pb)-induced oxidative damage, inflammation, and cholinergic dysfunction. Institute for Cancer Research (ICR) mice received Pb (II) acetate in drinking water (1%) with or without Cur via oral gavage. Blood and brain tissues were collected for investigation. Pb increased the inflammatory markers and oxidative parameters, which were ameliorated by Cur administration. Cur treatment also improved memory loss, learning deficit, and cholinergic dysfunction via elevating acetylcholinesterase (AChE) enzymatic activity and protein expression. In silico molecular docking supported the results; Cur had a potent binding affinity for AChE receptors, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), phosphorylations of IκB kinase (IKK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38). According to the chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, Cur could serve as a potential candidate for Pb detoxication substance via exerting antioxidant activity. Taken together, our results suggest that Cur is a natural compound that could be used for the treatment of neurodegenerative disorders via suppressing lead-induced neurotoxicity.

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

Pediatric primary mediastinal lymphoma – a descriptive study of a single cancer center of Bangladesh

Lymphomas involving the mediastinum occur in a wide age range and represent heterogeneous histological subtypes with various clinical symptoms and complex radiological findings. However, this cross sectional study that describes the clinical, pathological and radiological features of Bangladeshi pediatric patients aged less than 18 years. The study conducted in National Institute of Cancer Research and Hospital with 71 primary pediatric mediastinal masses, diagnosed between 2014 and 2018 and evaluated at enrollment or admission in the department of Pediatric Hematology and Oncology (PHO). The presence of extra thoracic lymph node involvement was excluded from the study. All patients were underwent computerized tomography (CT) or ultra sound (USG) guided needle biopsy. Only diagnosed cases of lymphoma (N-38) with mediastinal mass on chest radiography or CT scan were taken for analysis. Mediastinal lymphoma was 38 in number which, 16.30% of total (N-233) pediatric lymphoma of PHO. The median age of the patients was 11.43 years with mostly (68.42%) in 10-17 years age group. Males and females were equal in number. Common symptoms of the patients were fever, cough, dyspnea, chest pain. Most common side involved by tumors were anterior mediastinum 68.42% (N-26) followed by middle mediastinum 50% (N-19), Posterior mediastinum 10.53% (N-4) and superior mediastinum 7.9% (N-3). More than one mediastinal anatomical side involvement was in 34.21% (N-13) cases. Tissue biopsy revealed non Hodgkin Lymphoma were 86.84% (N-33), Hodgkin Diseases 10.53% (N-4) and T-lymphoblastic lymphoma (LBL) 2.63% (N-1). All tumors were malignant with 73.68% metastasis. Pediatric mediastinal mass is a troublesome condition for doctors during emergency management at presentation, for interventional radiologists during tissue biopsy, pathologists during histopathological examination and oncologists during treatment planning. A few publications narrated the pediatric mediastinal oncological conditions but in Bangladesh no such study has conducted before addressing the pediatric mediastinal lymphoma. So we conducted this study to show the importance of development of infrastructure to manage these type of tumors successfully.

An Audit to Evaluate the Assessment, Monitoring and Management of Cardiac Health in Patients Receiving Anti-HER2 Therapy for Breast Cancer – a Single Institution Experience

Purpose: This audit aimed to assess current standards with regards to the assessment and management of cardiac health in patients receiving anti-HER2 therapy. Therapeutic monoclonal antibodies to the HER2 receptor can also bind to myocytes expressing HER2, resulting in left ventricular dysfunction and clinical heart failure. Therefore, echocardiogram monitoring is essential [1]. Practice was assessed against the UK National Cancer Research Institute recommendations for prevention, monitoring and management of cardiac events in trastuzumab-treated patients [2].

Prospective Outcome Analysis of Adolescents and Young Adults Receiving Treatment from a Tertiary Cancer Hospital in Bangladesh

Background: Malignancies in adolescents and young adults (AYAs) are increasing day by day with increasing their death occurrences but a few clinical and epidemiological data from developing countries. There are 72006601.45(44.2%) people under this 15-39 years age group in Bangladesh. They are in vital age group not only for their own development but also for their country and for the world. This study was aimed to find out the outcome of treatment and causes of death. Methods: The study was an observational study. All histologically confirmed cancer patients aged 15-39 years who completed treatment under medical oncology department in National Institute of Cancer Research and Hospital (NICRH) from Jan.2016 to Dec.2017(24 months). Of them 593 patient were included for the study. Their follow up were taken over phone or departmental follow up registries up to May, 2019. Information was prospectively studied. Results: Total 593 patients were enrolled for this study. Of them, male(M) 295(49.75%), female(F)298(50.25%) and M: F=1:1.01. After follow up, it was documented that 170(28.67%) patients were untraceable whose 63(10.62%) patients had no contact number. Among the remaining patients 473, 170(35.94%) patients were died due to anorexia 162(95.3%), both nausea and vomiting 90(53%), pain and fever 65(38.24%), diarrhea 57(33.53%), respiratory distress 38(22.35%), cachexia 37(21.76%), bleeding and generalized swelling 18(10.60%), opportunistic infection 10(5.88%), stroke 3(1.176%), surgical complication 2(1.18%). Of the died patient’s male were 96, female was 74 and M: F death ratio was 1.3:1. The leading causes of death, according to specific disease, were lung cancer 11(61%), head neck cancer 12(57%), sarcoma 56(46%), GIT (gastrointestinal tract) cancer 39(40.63%) and leukemia 12(35%). Least death occurred in GCT (germ cell tumor) 1(4.34%) and lymphoma 7(9%). Alive patients were 240. Of them male were 84, female was 156 and the ratio was M:F=1:1.86. According to specific disease, the highest survival was in testicular malignancy 18(85.71%), breast cancer 88(71%), FGT (female genital tract) 26(70%), lymphoma 44(59%) and GIT malignancy 42(43.75%). Conclusion: In AYA the death occurrences were 170(35.94%) and tract out of follow up were 170(28.67%). This high death occurrence dangerously alarming for developing countries as youth are majority of total population in developing countries. So Methods should be searched to reduce the AYA death occurrences. TAJ 2021; 34: No-2: 108-113

Population attributable risk for colorectal and breast cancer in England, Wales, Scotland, Northern Ireland, and the United Kingdom.

The population attributable risk (PAR) is a statistic commonly used for quantifying preventability of cancer. We report here PAR estimates for the United Kingdom (UK) along with its constituent countries for up-to-date risk factor-attributable colorectal cancer (CRC) and breast cancer (BC), focusing on diet and nutrition related factors and tobacco (CRC) using representative national surveys. The PAR was calculated using established, modifiable risk factors by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR): physical activity, body mass index (BMI), alcoholic drinks, red meat, processed meat, dietary fiber, dietary calcium, as well as cigarette smoking for CRC, and physical activity, BMI, alcoholic drinks, and fruits and vegetable consumption for BC. National prevalence estimates and relative risks (RRs) for CRC and BC were obtained from meta-analyses or large pooled analyses. Based on eight dietary and lifestyle risk factors, the estimates for attributable cases of CRC for males and females, respectively, were as follows: England: 67% and 60%; Scotland: 68% and 59%, Wales: 66% and 61%; Northern Ireland: 67% and 61%; and UK: 67% and 60%. Excluding smoking, the PAR for the UK was 61% for men and 52% for women. Based on four dietary and lifestyle risk factors, the estimates for BC were as follows: England: 26%, Scotland: 27%; Wales: 25%; Northern Ireland: 26%; and UK: 27%. Up to 67% for CRC and 27% of BC were attributable to modifiable dietary and lifestyle factors in the UK. Moderate differences in PAR are observed between countries due to different prevalence of exposure to risk factors.

Adipose Dysfunction in Adulthood Insulin Resistance of Low-Birth Weight Mice: A Proteomics Study.

PurposeTo investigate changes in the protein expression profile of white adipose tissue in low-birth weight (LBW) mice with high-fat diets using tandem mass tag (TMT) and liquid chromatography-mass spectrometry (LC-MS/MS) and parallel reaction monitoring (PRM).MethodsInstitute of Cancer Research (ICR) mice were used to establish an LBW model using malnutrition during pregnancy. Male pups were randomly selected from LBW and normal-birth weight (NBW) offspring, then all given a high-fat diet. Blood glucose, serum insulin, total cholesterol (TC) and triglyceride (TG) levels were measured. The weight ratio of liver, muscle, and adiposity index were calculated. Hematoxylin and eosin staining was used to visualize adipose tissue morphology. Oil red O staining of liver and TG content of muscle were used to determine ectopic lipid deposition. TMT combined with LC-MS/MS was used to analyze protein expression in white adipose tissue. PRM and Western blot were used to verify the expression of CD36, SCD1, PCK1 and PPARγ.ResultsCompared with NBW mice, fasting blood glucose, insulin and HOMA-IR significantly increased in LBW mice, indicating insulin resistance and impaired glucose regulation; TC, TG, adipocyte size, and adiposity index were increased in LBW mice, suggesting obesity and disorder of lipid metabolism. We observed ectopic lipid deposition in liver and muscle. There were 996 differentially expressed proteins (DEPs) in the LBW/NBW groups. Peroxisome proliferator-activated receptor (PPAR) was a relatively important signaling pathway regulating metabolic process in functional enrichment analysis of DEPs. Up-regulated expression of CD36, SCD1, and PCK1 in the adipose tissue of LBW mice was observed through PPAR pathways cluster analysis. And PRM and Western blot assay validated the proteomics findings.ConclusionWhen exposed to high-fat diets, LBW mice exhibited insulin resistance and disorder of lipid metabolism compared with NBW mice. The expression of PPARγ was elevated, as well as upstream CD36, downstream SCD1 and PCK1 of the PPARγ in the adipose tissue of LBW mice. It was suggested that the activation in CD36/PPARγ/SCD1 and CD36/PPARγ/PCK1 pathways may induce adipose dysfunction, thereby increasing susceptibility to insulin resistance.

In Memoriam: Beatrice Mintz, PhD (1921–2022)

In Memoriam: Beatrice Mintz, PhD (1921–2022)

2,2',4,4'-Tetrabromodiphenyl ether disrupts spermatogenesis in mice by interfering with the ER-Nrf1-Tfam-mitochondria pathway.

2,2',4,4' -tetrabromodiphenyl ether (BDE47), a well-known endocrine disruptor of the estrogen receptor (ER) is toxic to the mitochondria and spermatogenesis. This study aimed to explore the mechanism of BDE47 on spermatogenesis in mammals. Adult male Institute of Cancer Research (ICR) mice were gavaged daily with BDE47 (0, 1, or 10mg/kg bw) for 8weeks. Testicular weight, sperm production and motility, morphology of spermatogenic cells, nuclear respiratory factor 1 (Nrf1) level, and its expression in testes were determined. In vitro, cell viability, and key molecules in the ER-Nrf1-mitochondrial transcription factor A (Tfam)-mitochondria pathway in the immortalized mouse spermatogonia line (GC1) were determined at 48h and 0-5h after exposure; RNA interference (RNAi) was also performed to verify that the decreased Nrf1 was associated with mitochondrial dysfunction and the impaired viability of germ cells. The results indicated that BDE47 impaired testis weight and spermatogenesis, impaired mitochondria and germ cells, and decreased Nrf1 in the testes of mice. In vitro, after 48h exposure, BDE47 reduced cell viability, Nrf1 protein, and mRNA of Nrf1, Tfam, ATP synthase subunit β (Atp5b), and cytochrome c oxidase subunit I (mt-CO1) in GC1 while also reducing mRNA of Nrf1 and Tfam promptly (from 1 to 5h) after exposure. Furthermore, Nrf1 RNA interference decreased viability and mitochondrial function in GC1. These results indicated that BDE47 disrupts spermatogenesis in mice, probably by interfering with the ER-Nrf1-Tfam-mitochondria pathway, and Nrf1 is a target molecule of BDE47 estrogen receptor.

Lessons in chromatin organization and gender equity in research: an interview with Susan Gasser.

In this interview, Professor Susan Gasser speaks with Storm Johnson, commissioning editor for Epigenomics, on her research on genome stability, epigenetic regulation and chromatin organization, as well as her work supporting women in research. Susan Gasser completed her BA at the University of Chicago, with an honors thesis in biophysics, and her PhD in biochemistry at the University of Basel in 1982, with Gottfried Schatz. She was a postdoc with Ulrich Laemmli at the University of Geneva, which initiated her career-long interest in chromosomes and chromatin structure. She established her own laboratory at the Swiss Institute for Experimental Cancer Research (ISREC) in 1986, focusing on chromatin organization in budding yeast, combining genetics, microscopy and biochemical approaches to understanding silent chromatin and telomeres. In 2001, she was named professor of molecular biology at the University of Geneva and expanded her laboratory's pioneering use of high-resolution time-lapse fluorescence microscopy to study single locus dynamics in the nucleus. From 2004 to 2019, Susan was the Director of the Friedrich Miescher Institute for Biomedical Research in Basel, where she also led a research group until the end of 2020. In Basel, she extended her research interests into heterochromatin in Caenorhabditiselegans. Her laboratory identified the mechanisms that position tissue-specific genesin the nuclei ofembryos and ofdifferentiated tissues, combining high throughput molecular analyses with cell biology to determine structure-function relationships in chromatin. Since January 2021, Susan Gasser has been professor invité at the University of Lausanne and Director of the ISREC Foundation, where she is helping shape the new Agora Institute of Translational Cancer Research. She was elected to the Académie de France, Leopoldina, European Molecular Biology Organization (EMBO), American Association for the Advancement of Science and Swiss Academy of Medical Sciences, and she received the French National Institute of Health and Medical Research (INSERM) International Prize in 2011, the Federation of European Biochemical Societies | EMBO Women in Science Award in 2012, the Weizmann Institute Women in Science Award in 2013 and honorary doctorates from the University of Lausanne, the University of Fribourg and Charles University in Prague. In Switzerland, she was the recipient of the Friedrich Miescher Award, the National Latsis Prize and the Otto Naegeli Award for the promotion of medical research. She participates in numerous review boards and advisory committees in Switzerland, across Europe and in Japan; she currently serves on the governing board of the Swiss Federal Institutes of Technology and the Swiss Science Council. From 2000 to 2004, she was vice chairperson, then chairperson of the EMBO Council. Susan led the Gender Committee of the Swiss National Science Foundation from 2014 to 2019 and initiated the Swiss National Science FoundationPrima program for the Promotion of women in academia. She has actively promotedthe careers of women scientists in Europe and Japan.

Editorial introductions.

Editorial introductions.

Bangladesh decentralises cancer care services to expand access to care.

The Minister of Health and Family Welfare of Bangladesh, Zahid Maleque, announced in an address at the National Cancer Research Institute and Hospital (Dhaka, Bangladesh) that health-care services—including cancer care services—in the country will be decentralised to reduce the additional burden of patients in the capital city of Dhaka, and to provide equal quality of medical services, as compared with the Dhaka-based hospitals, to all the parts of the country.

Evaluation of genotoxicity of ethanolic extracts of Platostoma palustre by micronucleus assay

Platostoma palustre (Pp) jelly is a traditional food. Pp has been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim of this study was to evaluate the ethanolic extracts of Pp’ genotoxicity. The ethanolic extracts of Pp by using 40% ethanol for extraction. Evaluation of genotoxicity of ethanolic extracts of Pp by micronucleus assay was performed in vivo. During the in vivo genotoxicity-evaluated experiment, the experimental animal’s clinical behavior, body weight (BW), food consumption, and the percentage of RET/RBCs (reticulocytes/red blood cells) and MN-RET/RETs (micronucleated reticulocytes/reticulocytes) after the treatments of Pp ethanolic extracts were evaluated. Both sexes Institute of Cancer Research (ICR) mice were given three daily treatments by intraperitoneal injection of 2 mg/kg of mitomycin C (genotoxicity induction) or by oral route of 200 μL of PBS (normal control group). Until 48 h after the last treatment, K2-EDTA-anticoagulated peripheral blood specimens were collected. These blood samples were processed for the microscopy-based analysis using Giemsa stain and the percentage of reticulocytes and micronucleated reticulocytes was determined. The results were shown that the experimental animal’s clinical behaviors were normal in all groups. The BW and food consumption were no significant difference between all groups. RET/RBCs (‰) in male or female ICR mice in the negative control group, the normal control group, the high dose of Pp ethanolic extract group, the middle dose of Pp ethanolic extract group, and the low dose of Pp ethanolic extract group were respectively 7.8 ± 0.8 / 8.6 ± 0.8, 23.2 ± 1.5 / 22.1 ± 1.3, 22.8 ± 1.6 / 22.1 ± 1.7, 23.2 ± 1.5 / 22.6 ± 1.0 and 22.2 ± 1.9 / 23.9 ± 1.9; MN-RET/RETs (‰) in male or female ICR mice in the negative control group, the normal control group, the high dose of Pp ethanolic extract group, the middle dose of Pp ethanolic extract group, and the low dose of Pp ethanolic extract group were 2.0 ± 0.0 / 2.0 ± 0.0, 43.2 ± 10.6 / 39.6 ± 10.9, 1.8 ± 0.4 / 1.6 ± 0.5, 1.6 ± 0.5 / 1.4 ± 0.5, and 1.8 ± 0.4 / 1.6 ± 0.5, respectively. Both RET/RBCs (‰) and MN-RET/RETs (‰) in male or female ICR mice in the negative control group were significantly difference than the other groups (p &lt; 0.001). Taken all results together, Pp ethanolic extracts were without genotoxicity. Therefore, Pp ethanolic extracts were safety.

Beatrice Mintz (1921-2022): an innovator in embryo research and cancer biology

Beatrice Mintz (1921-2022): an innovator in embryo research and cancer biology

Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.

Glossogyne tenuifolia (GT) is a native perennial plant growing across the coastline areas in Taiwan. The current study aimed to examine the efficacy of GT extract in ameliorating physical fatigue during exercise and increasing exercise performance. Fifty male Institute of Cancer Research (ICR) mice were randomly segregated into five groups (n = 10) to GT extract orally for 4 weeks, at different concentrations (50, 100, 250, and 500 mg/kg BW/day): LGT 1X, MGT 2X, HGT 5X, and HGT 10X groups. Forelimb grip strength, endurance swimming time, serum biochemical marker levels, blood lipid profile and histological analysis of various organs were performed to assess the anti-fatigue effect and exercise performance of GT extract. The forelimb-grips strength and endurance-swimming time of GT-administered mice were increased significantly in a dose-dependent manner when compared to the control. Serum glucose, creatine kinase, and lactate levels were increased significantly in the HGT 10X group. Liver marker serum glutamic-oxaloacetic transaminase (GOT) was increased in the HGT 5X and HGT 10X groups, whereas Serum Glutamic Pyruvic Transaminase (GPT) was not altered. Renal markers, creatinine and uric acid levels, were not altered. Muscle and hepatic glycogen levels, which are essential for energy sources during exercise, were also significantly increased in a dose-dependent manner in all GT extract groups. No visible histological aberrations were observed in the vital organs after GT extract administration. The supplementation with GT extract could have beneficial effects on exercise performance and anti-fatigue function without toxicity at a higher dose.

Suppressive Role of Lactoferrin in Overweight-Related Female Fertility Problems

The secretory glycoprotein lactoferrin (LF) is suggested to ameliorate overweight regardless of non-genetic or genetic mechanisms. Although maternal overweight represents a key predictor of offspring growth, the efficacy of LF on fertility problems in overweight and obese mothers remains unknown. To address this issue, we examined the effect of LF ingestion by analyzing overweight mice (Institute of Cancer Research (ICR) mice with high-fat diets; HF mice) and obese mice (leptin-deficient mice with type II diabetes; ob/ob mice). Plasma insulin, leptin, glucose, and cholesterol levels were measured, and thermal imaging and histological analysis were employed. The litter size of HF females was reduced due to miscarriage, which was reversed by LF ingestion. In addition, LF ingestion suppressed overweight prevalence in their offspring. The component analysis of the maternal blood demonstrated that glucose concentration in both HF females and their offspring was normalized by LF ingestion, which further standardized the concentration of insulin, but not leptin. LF ingestion was unable to reverse female infertility in ob/ob mice, although their obesity and uterine function were partially improved. Our results indicate that LF upregulates female fertility by reinforcing ovarian and uterine functions in females that are overweight due to caloric surplus.

Associations Between Unprocessed Red Meat and Processed Meat With Risk of Recurrence and Mortality in Patients With Stage III Colon Cancer

The American Cancer Society and American Institute for Cancer Research recommend that cancer survivors limit intake of red and processed meats. This recommendation is based on consistent associations between red and processed meat intake and cancer risk, particularly risk of colorectal cancer, but fewer data are available on red and processed meat intake after cancer diagnosis. To examine whether intake of unprocessed red meat or processed meat is associated with risk of cancer recurrence or mortality in patients with colon cancer. This prospective cohort study used data from participants with stage III colon cancer enrolled in the Cancer and Leukemia Group B (CALGB 89803/Alliance) trial between 1999 and 2001. The clinical database for this analysis was frozen on November 9, 2009; the current data analyses were finalized in December 2021. Quartiles of unprocessed red meat and processed meat intake assessed using a validated food frequency questionnaire during and 6 months after chemotherapy. Hazard ratios (HRs) and 95% CIs for risk of cancer recurrence or death and all-cause mortality. This study was conducted among 1011 patients with stage III colon cancer. The median (IQR) age at enrollment was 60 (51-69) years, 442 patients (44%) were women, and 899 patients (89%) were White. Over a median (IQR) follow-up period of 6.6 (1.9-7.5) years, we observed 305 deaths and 81 recurrences without death during follow-up (386 events combined). Intake of unprocessed red meat or processed meat after colon cancer diagnosis was not associated with risk of recurrence or mortality. The multivariable HRs comparing the highest vs lowest quartiles for cancer recurrence or death were 0.84 (95% CI, 0.58-1.23) for unprocessed red meat and 1.05 (95% CI, 0.75-1.47) for processed meat. For all-cause mortality, the corresponding HRs were 0.71 (95% CI, 0.47-1.07) for unprocessed red meat and 1.04 (95% CI, 0.72-1.51) for processed meat. In this cohort study, postdiagnosis intake of unprocessed red meat or processed meat was not associated with risk of recurrence or death among patients with stage III colon cancer.