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- Höglund, Odd, et al.
(författare)
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Online dosimetri för temoporfin-medierad interstitiell fotodynamisk terapi av prostata på hund
- 2012
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Ingår i: SUF-nytt. - 2001-3981. ; , s. 34-34
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Annan publikation (refereegranskat)abstract
- Bakgrund: Prostatacancer är vanligt förekommande hos män och orsakar fler dödsfall än andra cancerformer, förutom lungcancer. Ca 1 av 6 män får diagnosen prostatacancer under sin livstid (1, 2). Eftersom kirurgisk behandling och strålning av prostatavävnad orsakar biverkningar, framförallt impotens och inkontinens söks alternativa behandlingsmetoder. Interstitiell fotodynamisk terapi (PDT) är ett alternativ till att behandla tumöromvandlad prostatavävnad. Vid PDT bildas cytotoxiska radikaler som orsakar vävnadsnekros. Med hjälp av Spectracures P18-system erbjuds kontrollerad dosering av energimängden som överförs till prostatan. Syftet med denna studie var att verifiera korrelationen mellan energidos, vävnadsrespons och tröskeldos för induktion av nekros i prostata.Metod: Nio destinationsuppfödda friska beaglar användes i studien. Tre dagar före PDT gavs Temoporfin (Foscan) för fotosensibilisering. Med hjälp av transrektalt ultraljud bedömdes prostatans storlek och dosberäkning utfördes. Sju brakyterapinålar fördes in i prostatan via perineum under guidning av ultraljud och dosberäknad PDT utfördes. Sju dagar efter behandlingen avlivades hundarna.Resultat: Vid histopatologisk undersökning sågs nekroser i prostatan och förändringar i periprostata-vävnaden. En dos-responskorrelation för induktion av nekros bestämdes till 20-30 J/cm2. Online-dosimetri resulterade i mer fokuserad behandling och mindre skada på omkringliggande vävnad jämfört med PDT utan dosimetri.Konklusion: Denna studie visar att temoporfin-medierad interstitiell fotodynamisk terapi kan åstadkomma nekros av prostatavävnad. Metoden är en potentiell alternativ behandling till prostatektomi och brakyterapi.1. National Cancer Institute http://www.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-cancer-overview-key-statistics 2. American Cancer Society 2008 Cancer Facts and Figures
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- Cozzi, Elisabetta, et al.
(författare)
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Identification of long non-coding RNAs involved in leukemogenesis and venetoclax response in acute myeloid leukemia through functional CRISPR-dCas9 interference screens
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Acute myeloid leukemia (AML) is a malignant hematologic disease with poor prognosis. Increased understanding of disease biology is therefore needed to improve outcome for patients. While the protein-coding genome is well characterized in AML, knowledge about the involvement of non-coding genes is very limited in AML. Here, it was sought to investigate how long non-coding RNAs (lncRNAs) could contribute to disease biology and treatment resistance in AML. Three high-throughput lncRNA-CRISPR-interference screens were performed in MOLM-13 cells, knocking down about 8000 lncRNA expressed in hematopoietic cells. Effects on cell proliferation, cell differentiation and response to the anti-leukemic Bcl-2-inhibitor venetoclax were investigated upon lncRNA repression. LncRNAs most likely to positively or negatively regulate these processes were identified and top lncRNA candidates investigated with respect to expression in AML and healthy CD34+ cells and clinical AML correlations. Four lncRNAs involved in AML cell proliferation were identified (lncRNAs MIR17HG, CATG00000056335, CATG00000095269, CATG00000002239), two lncRNAs involved in differentiation (lncRNAs RP11-444A22.1, CATG00000058672) and seven lncRNAs implicated in venetoclax response. Among those, enhanced expression of proliferation-promoting lncRNA MIR17HG significantly correlated with poor outcome in AML patients (p= 0.03; p= 0.016). Further, lncRNA RP11-444A2 was identified as a predicted negative regulator of cell differentiation and was found to correlate with poor outcome (p=0.014). Further, lncRNA AC009299.3, predicted in venetoclax sensitivity, was found to be associated with poor outcome (p<0.0001), adverse risk (p=0.0014) and increased age (p=0.0045) in AML patients. Together, this study identified 14 lncRNAs proposed to be implicated in key leukemogenic events, highlighting their potential for elucidating AML biology, prognosis or treatment-response prediction and/or therapeutic use.
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- Daskalakis, Kosmas, et al.
(författare)
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Ex vivo activity of cytotoxic drugs and targeted agents in Small Intestinal NETs
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Small Intestinal Neuroendocrine Tumours (SI-NET) are considered to be generally resistant to systemic treatment. To date predictive markers for drug activity are lacking.Patients and Methods: Tumour samples from 27 patients with SI-NET were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinico-pathological variables and pre-treatment biomarkers.Results: For standard cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinums, gemcitabine and doxorubicin compared with CRC. For targeted kinase inhibitors, SI-NET was among the most sensitive diagnoses. CLL and ovarian cancer were generally the most sensitive diagnoses to both cytotoxic drugs and protein kinase inhibitors. The mTOR inhibitor sirolimus exhibited modest cytotoxic activity.Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors.Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo.Conclusions: SI-NETs exhibit variable but generally intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinico-pathological factors and currently used biomarkers were not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NETs. The great variability in drug sensitivity calls for individualized selection of therapy.
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- Frühling, Petter, et al.
(författare)
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Chemotherapy in patients with a singular colorectal liver metastasis : A nationwide propensity score matched study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionChemotherapy is widely used as an adjunct to surgery in the treatment of patients with resectable colorectal liver metastases. The aim of this study was to examine whether chemotherapy confers a survival benefit in patients with a singular colorectal liver metastasis. MethodsData were retrieved from National Quality of Registry for Liver, Bile Duct, and Gallbladder Cancer (SweLiv), and crosslinked with data from the Swedish Colorectal Cancer Registry (SCRCR). All consecutive patients who underwent a liver resection because of a resectable singular colorectal liver metastasis, between January 1, 2009 and December 31, 2017, were included. Patients treated with chemotherapy were compared with patients who had surgery alone. Unmatched and propensity score matched analyses were performed to compare overall survival, morbidity and mortality. ResultsOf 1224 eligible patients, 641 (52.4 per cent) patients had chemotherapy, and 583 (47.6 per cent) had surgery alone. After propensity score matching, two balanced groups with 102 patients in each, were analyzed. Median age was 69 years and 71 years in the chemotherapy and surgery alone groups, respectively. A majority of patients, in both groups, were men. Approximately, 80 per cent of patients belonged to ASA classification 1 or 2 (chemotherapy n= 78, surgery alone n =83), and tumor size was less than 30 mm in 70 per cent of patients in both groups. Eleven patients (10.8 per cent) in the surgery alone group had a tumor larger than 50 mm in diameter, and seven patients (6.9 per cent) in the chemotherapy group. There was no difference in readmission within 30-days (p=0.777), or morbidity, defined as Clavien-Dindo 3a or greater, between the groups (p= 0.761). There were no mortalities within ninety days. Radical resection margins were achieved in 92 (n=94) per cent in the chemotherapy group, and 77 (n=78) per cent in the surgery alone group (p=0.999). Median overall survival was 91 (73-109) months in the chemotherapy group, and 78 (37-119) months in the surgery-alone group (p=0.652). ConclusionThis nationwide register-based study showed no difference in overall survival between patients treated with chemotherapy compared to surgery alone. There was no difference in morbidity and mortality.
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