344 research outputs found
Parameter estimation of a bivariate diffusion process : the Heston model
No full textIncludes abstract.Includes bibliographical references (leaves 27-29).The main objective of the research is to estimate the parameters on the Heston (1993) model, which models the movement of asset prices assuming that the asset price volatility is stochastic. The paper concentrates on estimating these parameters by approximating the transitional probabilities of the diffusion process with a saddlepoint distribution. By solving a system of ordinary differential equations that are in terms of the system’s cumulants, and using these solutions to calculate the saddlepoint, the transitional probabilities of the diffusion process can be approximated
Comparison of standard dose and reduced dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review
No full textObjective: To review the efficacy and safety of low dose versus standard dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.Methods and Analysis: Keyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide. Searches were limited to original full-text and English language studies. Key outcomes included overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) response, and treatment-related adverse events. The review was performed in accordance with Cochrane Rapid Reviews Methods Group guidelines.Results: Ten studies were identified that met the eligibility criteria (PROSPERO number: CRD42023440371); five phase I studies, two post-hoc analyses of phase III trials, and three retrospective analyses. No consistent association between OS, PFS, and drug dose was identified. Fewer severe treatment-related adverse events were observed at lower drug doses.Conclusion: This review provides evidence that enzalutamide, apalutamide or darolutamide could be given at a lower than the standard recommended dose without loss of anti-tumour activity. A prospective near-equivalence randomised trial should be undertaken to compare registered and lower doses of these agents. <br/
Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab.
No full textBACKGROUND: We evaluated shedding of epidermal growth factor type II receptor (Her2/neu) extracellular domain (ECD) in primary uterine serous carcinoma (USC) cell lines and in the serum of USC patients and its biological effects in experiments of trastuzumab-induced cytotoxicity in vitro.
METHODS: Her2/neu expression was evaluated by immunohistochemistry (IHC), real-time PCR and flow cytometry, while c-erbB2 gene amplification was assessed using fluorescent in situ hybridisation (FISH). Her2/neu ECD levels in the supernatants of USC cell lines and in the serum of 38 USC patients and 19 controls were tested using ELISA. The biologic effect of Her2/neu ECD on trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated in 5-h chromium-release assays.
RESULTS: Five out of ten USC cell lines overexpressed Her2/neu by IHC and showed amplification of the c-erbB2 gene. High levels of Her2/neu ECD were found in supernatants of all FISH-positive tumours. In contrast, FISH-negative USC was negative for Her2/neu ECD shedding. Serum Her2/neu ECD levels in patients harbouring 3+Her2/neu tumours were higher than those found in healthy women (P=0.02) or USC patients with 2+ or 1+/negative Her2/neu expression (P=0.02). In cytotoxicity experiments, trastuzumab-mediated ADCC was significantly decreased by the addition of Her2/neu ECD-containing supernatants (P=0.01).
CONCLUSION: FISH-positive c-erbB2 USC cell lines shed high levels of Her2/neu ECD. High levels of Her2/neu ECD in USC patients may reduce trastuzumab-mediated ADCC in vitro and potentially neutralise its therapeutic effect in vivo. British Journal of Cancer (2011) 105, 1176-1182. doi:10.1038/bjc.2011.369 www.bjcancer.com Published online 13 September 2011 (C) 2011 Cancer Research U
Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study
No full textBACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue."Published version, accepted version (12 month embargo)Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Eradication of chemotherapy-resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of Clostridium perfringens enterotoxin.
No full textBACKGROUND: Emerging evidence has suggested that the capability to sustain tumor formation, growth, and chemotherapy
resistance in ovarian as well as other human malignancies exclusively resides in a small proportion of tumor
cells termed cancer stem cells. During the characterization of CD44þ ovarian cancer stem cells, we found a high
expression of the genes encoding for claudin-4. Because this tight junction protein is the natural high-affinity receptor
for Clostridium perfringens enterotoxin (CPE), we have extensively investigated the sensitivity of ovarian cancer
stem cells to CPE treatment in vitro and in vivo. METHODS: Real-time polymerase chain reaction and flow cytometry
were used to evaluate claudin-3/-4 expression in ovarian cancer stem cells. Small interfering RNA knockdown experiments
and MTS assays were used to evaluate CPE-induced cytotoxicity against ovarian cancer stem cell lines in vitro.
C.B-17/SCID mice harboring ovarian cancer stem cell xenografts were used to evaluate CPE therapeutic activity in
vivo. RESULTS: CD44þ ovarian cancer stem cells expressed claudin-4 gene at significantly higher levels than matched
autologous CD44 ovarian cancer cells, and regardless of their higher resistance to chemotherapeutic agents died
within 1 hour after exposure to 1.0 lg/mL of CPE in vitro. Conversely, small-interfering RNA-mediated knockdown of
claudin-3/-4 expression in CD44þ cancer stem cells significantly protected cancer stem cells from CPE-induced cytotoxicity.
Importantly, multiple intraperitoneal administrations of sublethal doses of CPE in mice harboring xenografts
of chemotherapy-resistant CD44þ ovarian cancer stem cells had a significant inhibitory effect on tumor progression
leading to the cure and/or long-term survival of all treated animals (ie, 100% reduction in tumor burden in 50% of
treated mice; P < .0001). CONCLUSIONS: CPE may represent an unconventional, potentially highly effective strategy
to eradicate chemotherapy-resistant cancer stem cells
The convenient determination of palladium at a solid electrode via adsorptive stripping voltammetry at a glassy carbon electrode modified with a random array of mercury nanodroplets
No full textThe detection of palladium using adsorptive stripping voltammetry reported by Wang et al. (J. Wang, K. Varughese Anal. Chim. Acta 1987, 199, 185 [3]) at a hanging mercury drop electrode is extended to a more convenient solid electrode. To this end a random array of 3.5×108 mercury nanodroplets per cm2 (65 nm average diameter) was electrodeposited on a glassy carbon substrate. Adsorptive stripping voltammetry was performed using 2×10-4 M dimethylglyoxime as a chelating agent for the Pd(II) ion, with accumulation at -0.20 V vs. SCE for 120 s and a linear detection range of 5–150 µM was determined with a limit of detection of 1.6 µM
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2916-21. doi: 10.1073/pnas.1222577110. Epub 2013 Jan 28. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Zhao S1, Choi M, Overton JD, Bellone S, Roque DM, Cocco E, Guzzo F, English DP, Varughese J, Gasparrini S, Bortolomai I, Buza N, Hui P, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Carrara L, Pecorelli S, Silasi DA, Ratner E, Azodi M, Schwartz PE, Rutherford TJ, Stiegler AL, Mane S, Boggon TJ, Schlessinger J, Lifton RP, Santin AD
No full textScreening of Traditionally Used Plants for in Vivo Antimalarial Activity in Mice.
No full textAqueous ethanol (80%) extracts of six plants used traditionally for treatment of malaria, Vepris glomerata (F.Hoffm.) Engl (Rutaceae), Maranthus floribunda (Bak.) F.White (Chrysobalanaceae), Strophanthus eminii Asch. & Pax ex Pax (Apocynaceae), Cassia abbreviata Oliv. (Leguminosae) and Caesalpinia bonducella L. Fleming (Fabaceae) were screened for antimalarial activity to establish validity of their claims. The extracts exhibited antimalarial activity in the 4-day Peter's suppressive antimalarial assay in mice inoculated with red blood cells parasitized with Plasmodium berghei. The extracts gave ID(50) values of 42.8, 111.0, 639.3 and 1560 mg/kg body wt for C. bonducella, C. abbreviata, T. furialis and S. eminii, respectively. The ID(50) values for V. glomerata and M. floribunda were above 2400 mg/kg body wt, above which point solubility was a problem. All the tested extracts were innocuous to the mice, up to 2400 mg/kg body wt, suggesting they may be safe for short-term use
Images in cardiovascular medicine : multiphoton microscopy for three-dimensional imaging of lymphocyte recruitment into apolipoprotein-E-deficient mouse carotid artery
No full textTwo recent elegant studies have shown that in apolipoprotein-E– deficient mice, the lamina adventitia is a major site of arterial wall inflammation associated with lymphocyte infiltration into atherosclerotic arteries and with formation of adventitial lymphoid-like tissues.1,2 These results suggest that lymphocyte responses in the lamina adventitia may play a crucial role in atherosclerosis development.1,
Breinlia (Johnstonema) woerlei Chabaud & Bain 1976
No full textBreinlia (Johnstonema) woerlei (Spratt & Varughese, 1975) Chabaud & Bain, 1976 (Figs. 78–81) Johnstonema woerlei Spratt & Varughese, 1975, pp. 17–20, figs. 13–20, from Petrogale brachyotis (syn. Petrogale venustula) Cannon Hill, Northern Territory. Breinlia (Johnstonema) woerlei (Spratt & Varughese) Chabaud & Bain, 1976, p. 378; Spratt et al. 1991, p. 38, 69. Type host. Petrogale brachyotis (Gould) (Marsupialia: Macropodidae). Site in host. Right ventricle and pulmonary arteries, lungs. Female and microfilariae undescribed. Other material examined. From right ventricle Petrogale brachyotis: NT : 1♀ (N428), from lung cysts and right ventricle, ♀♀ fragments (N3), (AHC 45885), (N5) Mt. Borradaile; 1♂ anterior & posterior, 4♀ (QM G232536), 3♀ (AHC 45886), 1♀ (AHC 45887) Narbalek. Differential diagnosis. Breinlia (Johnstonema) woerlei is distinguished from the other species in the subgenus B. (J.) annulipapillata (syn. B. (J.) andersoni) by the much larger size of males and females, the greater lengths of spicules in males, the clearly divided oesophagus and longer tail in females and the tissue location in the hosts. Description. General: Very long, exceptionally broad nematodes with markedly attenuated cephalic and caudal ends. Without cervical dilatation. Oral opening and cephalic extremity as described for males (Spratt & Varughese, 1975, p.18). Buccal capsule minute, with refractile ring at its base in males, not detected in females. Oesophagus divided into anterior muscular and posterior glandular regions. Excreteory pore not observed. Cuticle with prominent transverse annulations spaced at approximately 16 µm in males, 23 µm in females, longitudinally elongate, refractile cuticular bosses present in males, absent in females. Spicules long, stout, subequal, of complex, dissimilar morphology, heavily sclerotised. Deirids and phasmids not observed. Male: (one anterior and one posterior fragment from P. brachyotis). MW 630. NR 249. MO 450, GO 1060. LS 609, not distinctly divided into calomus, lamina and filament, navicular, with in–rolled edges and bluntly rounded distal extremity. RS 450, tubular proximally, with spatulate distal extremity. T 2120, curved ventrally, with 2 pairs papillae, an asymmetric pair ventrally 162 µm from tail tip and a terminal pair. Cloacal papillae 10 in number, not restricted to cloacal region. Female: (Measurements of complete specimen presented first in italics followed by mean and range of fragments of 8 others). BL 162 mm, longest fragment 260 mm. MW 948, 1106 (948–1264) in mid–body. NR 1 98, 268 (185–345). MO 345, 464 (371–556), GO 954, 1272(1166–1590), oesophago–intestinal junction sometimes hidden by anterior loops of uterus and/or vagina filled with microfilariae. V 6162, 6241 (5530–6952) from anterior extremity. T 1457, 1290–1930, markedly attenuated, with two, large latero–ventral papillae and pair of small median terminal papillae. Microfilaria (5 specimens from uterus). BL 221 (216–223) long. MW 6 (5–6). Tail tapering, filamentous terminally. Unsheathed. Site in host unknown. Distribution and hosts. Breinlia (Johnstonema) woerlei is known only from Petrogale brachyotis from the Arnhem Land region of the Northern Territory. Remarks. Spratt and Varughese (1975) described and illustrated only the male of B. (J.) woerlei from Petrogale brachyotis (syn. P. venustula).This is the first description of the female of the species, one of the largest filarioids known from one of the smallest macropodid marsupials and rivalling in size Breinlia (Breinlia) ventricola Spratt & Hobbs, 2003 from the right ventricle and pulmonary arteries of the largest macropodid marsupial, the red kangaroo, Macropus rufus, in the southern Pilbara region of Western Australia. While there have been no studies of the pathological effects of these nematodes on their rock wallaby hosts, their location in the right ventricle and pulmonary arteries as well as in cysts in the lungs must have a profound effect on the function of these organs. As Spratt and Hobbs (2003) noted in their discussion of B. (B.) ventricola in red kangaroos, it is expected that many aspects of the pathology seen in canine dirofilariasis would occur in rock wallabies infected with B. (J.) woerlei, including pulmonary hypertension, impaired heart valve function and physical blockage (Knight 1977). To date, only females have been recovered from lung cysts.Published as part of Spratt, David M., 2011, New records of filarioid nematodes (Nematoda: Filarioidea) parasitic in Australasian monotremes, marsupials and murids, with descriptions of nine new species 2860, pp. 1-61 in Zootaxa 2860 (1) on pages 43-45, DOI: 10.11646/zootaxa.2860.1.1, http://zenodo.org/record/528650
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