• Flogging a dead salmon? reduced dose posterior to prostate correlates with increased PSA progression in voxel-based analysis of 3 randomized phase 3 trials

      Shortall, Jane; Palma, G.; Mistry, Hitesh; Vasquez Osorio, Eliana; McWilliam, Alan; Choudhury, Ananya; Aznar, Marianne Camille; van Herk, Marcel; Green, Andrew; Division of Cancer Science, University of Manchester, Manchester, United Kingdom. (2021)
    • Flow cytometric DNA characteristics of radiation colitis--a preliminary study.

      Pearson, J M; Kumar, Shant; Butterworth, D M; Schofield, Philip F; Haboubi, Najib; Department of Histopathology, University Hospital of South Manchester, West Didsbury, England. (1992)
      The DNA status of 12 rectal biopsies, taken during the investigation of radiation proctitis, was investigated. Of these six were in the acute phase and six in the chronic phase. All of the acute biopsies had diploid DNA, despite bizarre histological epithelial cell appearances. Two of the chronic phase biopsies were to have aneuploid DNA profiles. This finding may be relevant to the increased risk of malignancy in irradiated tissues.
    • Fludarabine phosphate for the treatment of low grade lymphoid malignancy.

      Whelan, J S; Davis, C L; Rule, S; Ranson, Malcolm R; Smith, O P; Mehta, A B; Catovsky, D; Rohatiner, A Z; Lister, T A; ICRF Department of Medical Oncology, St Bartholomew's Hospital, London, UK. (1991-07)
      Thirty-four patients with previously treated, advanced, low grade NHL were treated with Fludarabine, a deamination-resistant analogue of adenosine arabinoside, at a dose of 25 mg m-2 intravenously, daily for 5 days (median number of cycles = 3, range 1-10). Complete remission (CR) was achieved in six and partial remission (PR) in a further seven. Overall, responses were seen in 11/23 patients (48%) with follicular lymphoma and in 2/11 (18%) with low grade, diffuse NHL. Fifteen patients with previously treated CLL and one patient with prolymphocytic leukaemia (PLL) were also treated as above (median no. of cycles = 3, range 1-6). A partial response was seen in three of the 11 evaluable patients with CLL and CR was achieved in the patient with PLL. There were four deaths due to infection and 19 further episodes requiring admission to hospital. No other significant toxicity was reported in a total of 164 cycles of Fludarabine. This agent is active in advanced low grade lymphoid malignancy. Further studies are required to assess its role in newly diagnosed patients.
    • Fluorescent location of cells of cytological interest in cervical smears prestained with thionin.

      Steven, F S; Desai, Mina; Sin, J; Palcic, B; Division of Biochemistry, School of Biological Sciences, University of Manchester, U.K. (2010-04-08)
      Cervical cells of cytological interest were located in conventional smears, treated with thionin for quantitative DNA staining by subsequent treatment with fluorescent probes for a cell surface protease. Normal mature cervical epithelial cells failed to bind these fluorescent probes whilst metaplastic cells, glandular cells, and dyskaryotic cells were readily located. By this means, the nuclear staining of these fluorescent cells of cyotological interest enabled them to be classified by a cytologist.
    • Fluorescent location of malignant cells in fine needle aspirates.

      Steven, F S; El-Teraifi, H; Denton, J; Markidou, S G; Delinassios, J G; Division of Biochemistry, School of Biological Sciences, University of Manchester, Manchester M13 9PT, U.K. (2000)
      Malignant cells in fine needle aspirates possess a cell surface protease which can be targeted with fluorescent affinity probes. Cells with active GB exhibit cell surface fluorescence when stained with such affinity probes. The nuclei of all cells on the slides can be counterstained with a nuclear fluorescent stain. Malignant cells are then located by their cell surface fluorescence and their diagnosis confirmed by examining their fluorescent nuclei. Normal cells and benign cells exhibit no cell surface fluorescence and can be ignored. This technique can be used to rapidly select cells of cytological interest in FNA samples obtained routinely and might be adapted for automated screening of FNA.
    • Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion.

      Freeman, K; Connock, M; Cummins, E; Gurung, T; Taylor-Phillips, S; Court, R; Saunders, Mark P; Clarke, A; Sutcliffe, P; Warwick Medical School, University of Warwick, Coventry (2015-11)
      5-Fluorouracil (5-FU) is a chemotherapy used in colorectal, head and neck (H&N) and other cancers. Dose adjustment is based on body surface area (BSA) but wide variations occur. Pharmacokinetic (PK) dosing is suggested to bring plasma levels into the therapeutic range to promote fewer side effects and better patient outcomes. We investigated the clinical effectiveness and cost-effectiveness of the My5-FU assay for PK dose adjustment to 5-FU therapy.
    • Focal rhabdomyosarcomatous differentiation in primary liposarcoma.

      Shanks, Jonathan H; Banerjee, Saumitra S; Eyden, Brian P; Department of Histopathology, Christie Hospital NHS Trust, Withington, Manchester. (1996-09)
      A unique case of primary myxoid liposarcoma of the thigh, in which focal pleomorphic areas were present containing rhabdomyoblasts, is described. Focal rhabdomyosarcoma in liposarcoma has only rarely been reported previously and only in dedifferentiated liposarcomas of the retroperitoneum. All but one have been recurrences with rhabdomyoblasts being absent in the primary liposarcoma. As rhabdomyoblasts were only focally present, the present case is regarded as liposarcoma with focal divergent rhabdomyoblastic differentiation rather than malignant mesenchymoma.
    • Foci of amorphous/granulofilamentous matrix in the extracellular domain of tumours. 2. Immunohistochemical and immunogold characterization of a fibronectin-rich matrix component.

      Eyden, Brian P; Shore, Ian; Moss, Jill; Yamazaki, Kazuto; Ru, Y; Shanks, Jonathan H; Banerjee, Saumitra S; Department of Histopathology, Christie Hospital, Manchester, United Kingdom. brian.eyden@christie-tr.nwest.nhs.uk (2005-04)
      The term FEAM (foci of extracellular amorphous matrix) has been used for discretely outlined areas of moderately dense material having a filamentous/granular substructure located in the extracellular matrix of tumours. In spite of being widespread in mesenchymal tumours especially, and often abundant, they have received little attention in terms of structure, composition and origin. Mostly, they have been regarded as a variant or a product of lamina ('basement membrane material'). However, they also appear in tumours whose cells should and do lack a lamina, such as giant-cell fibroblastoma and solitary fibrous tumour. This paper describes their fine structure in a variety of predominantly mesenchymal tumours, and documents their composition using light microscope immunostaining and immunogold labelling. Small amounts of type IV collagen and laminin were found focally and inconsistently among the five tumours by light microscope immunostaining, but fibronectin was strongly and consistently identified. Strong fibronectin staining was also identified by immuno-electronmicroscopy. These data suggest that FEAM represent a fibronectin-rich matrix constituent, which might be a common final product of either lamina or the external component of the subplasmalemmal linear density (focal adhesion). There is little support light microscopically for a relationship to immune-complexes or cryoglobulins.
    • Foci of amorphous/granulofilamentous matrix in the extracellular domain of tumours: a study of 34 cases. 1. Ultrastructural characterisation.

      Eyden, Brian P; Ru, Y; Department of Histopathology, Christie Hospital NHS Trust, Manchester, UK. brian.eyden@christie-tr.nwest.nhs.uk (2003-04)
      The distribution and the appearance of foci of extracellular amorphous/granulofilamentous material (FEAM) in 34 human tumours are described. FEAM were rounded to oval, or more elongated or irregular elements of discretely delineated dense material lying in the extracellular space of tumours. They varied in size and abundance, sometimes coalescing into more extensive areas of dense material. At high magnification, FEAM exhibited a granular and finely filamentous substructure. Variations in the electron-density of FEAM were noted. Some FEAM were found associated with the surfaces of tumour cells, on occasion with subplasmalemmal linear densities. FEAM was also sometimes associated with matrix filaments, often collagen. Material of similar substructure and density was also associated with some vessels. FEAM were mostly found in tumours showing mesenchymal differentiation. The nature and origin of FEAM is discussed.
    • Focused VHEE (very high energy electron) beams and dose delivery for radiotherapy applications

      Whitmore, L.; Mackay, Ranald I; van Herk, Marcel; Jones, J. K; Jones, R. M.; Department of Physics and Astronomy, University of Manchester, Manchester, UK. (2021)
      This paper presents the first demonstration of deeply penetrating dose delivery using focused very high energy electron (VHEE) beams using quadrupole magnets in Monte Carlo simulations. We show that the focal point is readily modified by linearly changing the quadrupole magnet strength only. We also present a weighted sum of focused electron beams to form a spread-out electron peak (SOEP) over a target region. This has a significantly reduced entrance dose compared to a proton-based spread-out Bragg peak (SOBP). Very high energy electron (VHEE) beams are an exciting prospect in external beam radiotherapy. VHEEs are less sensitive to inhomogeneities than proton and photon beams, have a deep dose reach and could potentially be used to deliver FLASH radiotherapy. The dose distributions of unfocused VHEE produce high entrance and exit doses compared to other radiotherapy modalities unless focusing is employed, and in this case the entrance dose is considerably improved over existing radiations. We have investigated both symmetric and asymmetric focusing as well as focusing with a range of beam energies.
    • FOENIX-101: a phase II trial of TAS-120 in patients with intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements

      Goyal, L; Bahleda, R; Furuse, J; Valle, Juan W; Moehler, MH; Oh, DY; Chang, HM; Kelley, RK; Javle, MM; Borad, MJ; et al. (2019)
    • FOENIX-CCA2 quality of life data for futibatinib-treated intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions/rearrangements

      Valle, Juan W; Hollebecque, A.; Furuse, J.; Goyal, L.; Meric-Bernstam, F.; Epstein, R. S.; Salimi, T.; Wacheck, V.; Liu, M.; Benhadji, K. A.; et al. (2021)
      Background: In FOENIX-CCA2 (NCT02052778), a pivotal phase 2 study among iCCA patients (pts) with FGFR2 fusions/rearrangements, the highly selective, irreversible FGFR1–4 inhibitor futibatinib demonstrated a confirmed objective response rate of 41.7%, with a 9.7-month median duration of response. Adverse events were manageable with dosing modifications that did not adversely impact on response. We report outcomes for the preplanned analysis of Patient-Reported Outcomes (PROs) during futibatinib treatment as a secondary objective of FOENIX-CCA2. Methods: Pts enrolled in FOENIX-CCA2 had locally advanced/metastatic unresectable iCCA with FGFR2 fusions/rearrangements, ≥1 prior line of therapy (including gemcitabine/cisplatin) and ECOG PS 0-1. Pts received oral futibatinib 20 mg continuous QD dosing per 21-day cycle. PRO measures included EORTC-QLQ-C30 (1 global health, 5 functional, 9 symptom scales), EQ-5D-3L, and EQ visual analogue scale (VAS). PROs were collected at screening, cycles 2 and 4, every 3 cycles thereafter, and end of treatment. PRO data were evaluated up to cycle 13, the last visit before data were missing for >50% of the PRO population (PRO primary assessment time point). Results: 92/103 (89.3%) pts enrolled had PRO completion data at baseline and a minimum of 1 follow-up assessment (median age 58 y, 56.5% female), with 48 pts having PRO data at cycle 13. At baseline, mean (SD) EORTC QLQ-C30 global health status score was 70.1 (19.4) and EQ VAS score 71.7 (20.3). Mean EORTC QLQ-C30 global health status scores were maintained from baseline to cycle 13, corresponding to 9.0 months on treatment, with no clinically meaningful (≥10-point) changes in individual functional measures (Table). EORTC QLQ-C30 scores across individual symptom measures were also stable from baseline through cycle 13; only constipation showed an average of 10.0-point worsening at only cycle 4. Mean EQ VAS scores were sustained from baseline to cycle 13 (mean change ranging -1.8 to +4.8 across cycles), with values maintained within the population norm range from across 20 countries. Conclusions: Quality of life data from the phase 2 FOENIX-CCA2 trial show that physical, cognitive and emotional functioning, and overall health status were maintained among pts with advanced iCCA receiving futibatinib.
    • FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements

      Goyal, L.; Meric-Bernstam, F.; Hollebecque, A.; Valle, Juan W; Morizane, C.; Karasic, T. B.; Furuse, J.; He, Y. H.; Soni, N.; Benhadji, K. A.; et al. (2020)
      Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 (FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ?1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ?6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ?3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ?3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ?3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information:
    • Foetal and cancer patient fibroblasts produce an autocrine migration-stimulating factor not made by normal adult cells.

      Schor, Seth L; Schor, Ana M; Grey, A; Rushton, Graham; Department of Cell and Structural Biology, University of Manchester, England. (1988-07)
      We have previously reported that (1) the migration of foetal and adult fibroblasts into three-dimensional collagen matrices is differentially affected by cell density, and (2) skin fibroblasts from cancer patients commonly display a foetal-like mode of migratory behaviour. Data presented here indicate that differences in the migration of these cell types are particularly apparent in cultures plated at high density (i.e. at cell confluence); under these conditions, foetal fibroblasts and the foetal-like fibroblasts of cancer patients migrate into the three-dimensional collagen matrix to a significantly greater extent than do normal adult cells. In this initial study concerned with the biochemical basis of these observations, we report that medium conditioned by either foetal or cancer patient fibroblasts stimulates the migration of confluent adult cells. This stimulation of migration is specific to confluent cells, as the migration of subconfluent adult fibroblasts is unaffected by these conditioned media. Gel filtration chromatography of foetal fibroblast-conditioned medium indicates that migration-stimulating activity is recovered in a single peak with an apparent molecular mass in the range of 50-60 (X 10(3]. The active migration stimulating factor (MSF) in both foetal and cancer patient fibroblast-conditioned media appears to be a protein stable at acid pH, but inactivated by heat, alkaline pH and reductive alkylation. MSF produced by foetal and cancer patient fibroblasts is presumably responsible for the characteristically elevated levels of migration displayed by these cells in confluent culture, thereby suggesting an autocrine mode of action for this factor.(ABSTRACT TRUNCATED AT 250 WORDS)
    • FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience.

      Chllamma, M; Cook, Natalie; Dhani, N; Giby, K; Dodd, A; Wang, L; Hedley, D; Moore, M; Knox, J; Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto (2016-09-06)
      FOLFIRINOX has been shown to significantly increase both overall survival (OS) and progression-free survival (PFS) in metastatic pancreas cancer. There is limited data regarding the treatment of locally advanced pancreatic cancer. We present a retrospective study of patients with both locally advanced and metastatic pancreas cancer using FOLFIRINOX as first-line therapy in our centre.
    • FOLFIRINOX or FOLFOXIRI in locally advanced duodenal adenocarcinoma: are we missing out?

      Lamarca, Angela; Foster, L.; Valle, Juan W; Satyadas, T.; Siriwardena, A.; Department of Medical Oncology, The Christie NHS Foundation Trust; Division of Cancer Sciences, University of Manchester, Manchester, UK. (2020)
    • Folic acid supplementation in postmenopausal women with hot flushes: Phase III randomised double-blind placebo-controlled trial

      Ewies, A. A. A.; Ahmed, I.; Al-Azzawi, F.; Pitkin, J.; Gupta, P.; Persic, M.; Sahu, B.; El-Ghobashy, A.; Barraclough, Lisa H; Woodman, J.; et al. (2021)
      Objective: To assess whether folic acid supplementation ameliorates hot flushes. Design: Double-blind, placebo-controlled randomised trial. Setting: Nine hospitals in England. Population: Postmenopausal women experiencing ≥50 hot flushes weekly. Methods: Women (n = 164) were randomly assigned in a 1:1 ratio to receive folic acid 5 mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in a Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-week intervals. Main outcome measures: The change in daily Hot Flush Score at week 12 from randomisation based on Sloan Diary Composite Score B calculation. Results: Data of 143 (87%) women were available for the primary outcome. The mean change (SD) in Hot Flush Score at week 12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI -5.68 to 0.87) (P = 0.149) and in the adjusted mean change -2.61 (95% CI -5.72 to 0.49) (P = 0.098). Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week 8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI 1.16-9.28) and 1.88 (95% CI 0.23-3.52) for total and emotional score, respectively. Conclusions: The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo.
    • The Folie à trois.

      Mitin, T; Choudhury, Ananya; Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon (2017-09-01)
    • Follicle-stimulating hormone-dependent estrogen secretion by rat Sertoli cells in vitro: modulation by calcium.

      Talbot, J A; Lambert, A; Mitchell, R; Grabinski, M; Anderson, D C; Tsatsoulis, Agathocles; Shalet, Stephen M; Robertson, W R; Department of Medicine (Clinical Biochemistry), University of Manchester, Hope Hospital, Salford, UK. (1991-09)
      We have investigated the role of Ca2+ in the control of FSH-induced estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Exogenous Ca2+ (4-8 mmol/l) inhibited FSH-stimulated E2 secretion such that, with 8 mmol/l Ca2+ and FSH (8 IU/l) E2 secretion decreased from 2091 +/- 322 to 1480 +/- 84 pmol/l (p less than 0.002), whilst chelation of Ca2+ in the culture medium with EGTA (3 mmol/l) increased E2 secretion from 360 +/- 45 to 1242 +/- 133 pmol/l) in the absence of FSH. Further, EGTA (3 mmol/l) markedly potentiated FSH (8 IU/l), forskolin (1 mumol/l) and dibutyryl cAMP (1 mmol/l)-stimulated E2 secretion. Addition of the Ca2+ ionophores, ionomycin (2-5 mumol/l) and A23187 (2 mumol/l), inhibited FSH (8 IU/l)-stimulated E2 secretion by greater than 80%. The effect of ionomycin was totally reversible, whereas that of A23187 was irreversible. Ionomycin (5 mumol/l) had no effect on EGTA-induced E2 secretion in the absence of FSH, but reduced EGTA-provoked E2 secretion by 59% in the presence of FSH (8 IU/l). Similarly, forskolin- and dibutyryl cAMP-provoked E2 production was inhibited 46-50% by ionomycin (5 mumol/l). We conclude that FSH-induced E2 secretion from immature rat Sertoli cells is modulated by intra- and extracellular Ca2+.
    • Follicular dendritic cell sarcoma: a rare tumor presenting as an abdominal mass.

      Low, S E; Menasce, Lia P; Manson, C M; Department of Histopathology, Warrington Hospital, Warrington, England. preciousdumpling@doctors.org.uk (2007-07)
      Follicular dendritic cell (FDC) sarcoma is a rare and probably even underreported entity. Only approximately some 50 cases have been described in the literature, the majority of which had a lymph node origin. The authors report a case of FDC sarcoma arising within the soft tissues of the abdominal cavity. As FDC markers are often not routinely included in antibody panels, awareness of this sarcoma is important, as it can be confused with other tumors, especially when occurring extranodally.