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Nygren, Peter
Publications (10 of 135) Show all publications
Forslund, M., Nygren, P., Ottenblad, A. & Johansson, B. (2020). Experiences of a nutrition intervention: A qualitative study within a randomised controlled trial in men undergoing radiotherapy for prostate cancer. Nutrition & Dietetics, 77(2), 223-230
Open this publication in new window or tab >>Experiences of a nutrition intervention: A qualitative study within a randomised controlled trial in men undergoing radiotherapy for prostate cancer
2020 (English)In: Nutrition & Dietetics, ISSN 1446-6368, E-ISSN 1747-0080, Vol. 77, no 2, p. 223-230Article in journal (Refereed) Published
Abstract [en]

AIM: Men with prostate cancer undergoing radiotherapy may experience acute and late bowel symptoms. Nutrition interventions have shown some benefits, however, adherence tends to decline over time. Qualitative studies, carried out after an intervention, are important to help explain trial results. The aim of the present study was to explore patient experience of participating in a nutrition intervention in a randomised controlled trial, with a focus on facilitators and barriers to adherence.

METHODS: Semistructured interviews were conducted with 15 men with prostate cancer recruited from a randomised controlled trial on a nutrition intervention during radiotherapy. Interviews were analysed with content analysis with an inductive approach.

RESULTS: The informants were motivated to make dietary changes to avoid bowel symptoms. Social support, a feeling of contributing to the greater good, prior knowledge, dietary information and a small need for behaviour change facilitated adherence. Feeling limited, wanting to decide for themselves, the timing of the intervention, unmet expectations of dietary advice and loss of motivation, were described as barriers for adherence.

CONCLUSIONS: Future nutrition intervention trials may benefit from involving significant others to a greater degree, as well as offering pre-set recipes and strategies to manage social events, and more sessions with the dietitian for patients in need of more support. Tailored interventions based on the individual's preferences, context and prior knowledge about food may further facilitate adherence.

Keywords
experiences, interview, nutrition intervention, prostate cancer, radiotherapy
National Category
Nursing
Research subject
Caring Sciences
Identifiers
urn:nbn:se:uu:diva-399826 (URN)10.1111/1747-0080.12564 (DOI)000522619200007 ()31243870 (PubMedID)
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2020-05-07Bibliographically approved
Rendo, V., Stoimenov, I., Mateus, A., Sjöberg, E., Svensson, R., Gustavsson, A.-L., . . . Sjöblom, T. (2020). Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy. Nature Communications, 11, Article ID 1308.
Open this publication in new window or tab >>Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy
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2020 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 11, article id 1308Article in journal (Refereed) Published
Abstract [en]

Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound. Cancer chemotherapy targeting frequent loss of heterozygosity events is an attractive concept, since tumor cells may lack enzymatic activities present in normal constitutional cells. To find exploitable targets, we map prevalent genetic polymorphisms to protein structures and identify 45 nsSNVs (non-synonymous small nucleotide variations) near the catalytic sites of 17 enzymes frequently lost in cancer. For proof of concept, we select the gastrointestinal drug metabolic enzyme NAT2 at 8p22, which is frequently lost in colorectal cancers and has a common variant with 10-fold reduced activity. Small molecule screening results in a cytotoxic kinase inhibitor that impairs growth of cells with slow NAT2 and decreases the growth of tumors with slow NAT2 by half as compared to those with wild-type NAT2. Most of the patient-derived CRC cells expressing slow NAT2 also show sensitivity to 6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine (APA) treatment. These findings indicate that the therapeutic index of anti-cancer drugs can be altered by bystander mutations affecting drug metabolic genes.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-345963 (URN)10.1038/s41467-020-15111-4 (DOI)000520964700003 ()32161261 (PubMedID)
Funder
Swedish Cancer Society, 2018/772Swedish Research Council, 2016-01890Swedish Foundation for Strategic Research , F06-0050Swedish Foundation for Strategic Research , RBa08-0114Swedish Society for Medical Research (SSMF)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2020-04-17Bibliographically approved
Mody, K., Mansfield, A. S., Vemireddy, L., Nygren, P., Gullbo, J. & Borad, M. (2019). A phase I study of the safety and tolerability of VLX600, an Iron Chelator, in patients with refractory advanced solid tumors. Investigational new drugs, 37(4), 684-692
Open this publication in new window or tab >>A phase I study of the safety and tolerability of VLX600, an Iron Chelator, in patients with refractory advanced solid tumors
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2019 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 37, no 4, p. 684-692Article in journal (Refereed) Published
Abstract [en]

Introduction VLX600 is a novel iron chelator designed to interfere with intracellular iron metabolism, leading to inhibition of mitochondrial respiration and bioenergetic catastrophe and resultant tumor cell death. Methods We conducted a multicenter, phase 1, dose escalation study to determine the safety and adverse event profile and the maximum tolerated dose and recommended phase 2 dose of VLX600. Other endpoints included pharmacokinetics, and preliminary evidence of anti-cancer efficacy as assessed according to RECIST 1.1 criteria. VLX600 was administered intravenously on days 1, 8, and 15 of each 28-day treatment cycle. Results Nineteen patients were enrolled, and seventeen received at least one dose of VLX600. Dose increments were reduced to 50% after dose level 3 (40mg) due to the occurrence of a grade 3 pulmonary embolism. The study was then closed early due to slow recruitment. No maximum tolerated dose (MTD) nor RP2D had been identified at the time of study closure. Overall, the drug was well tolerated and no DLTs were observed. Fourteen patients experienced drug-related adverse events of any grade. The most frequently reported drug-related AEs were fatigue, nausea, constipation, vomiting, increased alkaline phosphatase, anemia, and decreased appetite. No formal efficacy or survival analyses were performed. No objective responses were observed, though six patients (32%) had stable disease as best response. Conclusion VLX600 was reasonably well tolerated and, together with preclinical data, there is support for further efforts to explore its activity as single agent and in combination with drugs or radiation.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Clinical trial, Phase 1, Iron chelating agents, VLX600
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390390 (URN)10.1007/s10637-018-0703-9 (DOI)000475627500010 ()30460505 (PubMedID)
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Glimelius, B. & Nygren, P. (2019). Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer. Acta Oncologica, 58(4), 395-397
Open this publication in new window or tab >>Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer
2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 4, p. 395-397Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-382767 (URN)10.1080/0284186X.2019.1584405 (DOI)000463726300001 ()30882261 (PubMedID)
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved
Månsson, C., Brahmstaedt, R., Nygren, P., Nilsson, A., Urdzik, J. & Karlson, B.-M. (2019). Percutaneous Irreversible Electroporation as First Line Treatment of Locally Advanced Pancreatic Cancer. Anticancer Research, 39(5), 2509-2512
Open this publication in new window or tab >>Percutaneous Irreversible Electroporation as First Line Treatment of Locally Advanced Pancreatic Cancer
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2019 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 5, p. 2509-2512Article in journal (Refereed) Published
Abstract [en]

Background/Aim:

Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates.

Patients and Methods:

Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison.

Results:

The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment.

Conclusion:

No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.

Keywords
Pancreatic Neoplasms, Electroporation, Interventional Ultrasonography
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365201 (URN)10.21873/anticanres.13371 (DOI)000469427800032 ()31092446 (PubMedID)
Available from: 2018-11-11 Created: 2018-11-11 Last updated: 2019-06-26Bibliographically approved
Bjorke, A. C., Sweegers, M. G., Buffart, L. M., Raastad, T., Nygren, P. & Berntsen, S. (2019). Which exercise prescriptions optimize V̇O2max during cancer treatment?: a systematic review and meta-analysis. Scandinavian Journal of Medicine and Science in Sports, 29(9), 1274-1287
Open this publication in new window or tab >>Which exercise prescriptions optimize V̇O2max during cancer treatment?: a systematic review and meta-analysis
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2019 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 29, no 9, p. 1274-1287Article, review/survey (Refereed) Published
Abstract [en]

The aims of the present systematic review and meta-analysis were to investigate the effect of exercise on maximal oxygen uptake ((V) over dot O(2)max) and to investigate whether exercise frequency, intensity, duration, and volume are associated with changes in (V) over dotO(2)max among adult patients with cancer undergoing treatment. Medline and Embase through OvidSP were searched to identify randomized controlled trials. Two reviewers extracted data and assessed the risk of bias. The overall effect size and differences in effects for different intensities and frequencies were calculated on change scores and post-intervention (V) over dot O(2)max data, and the meta-regression of exercise duration and volumes was analyzed using the Comprehensive Meta-Analysis software. Fourteen randomized controlled trials were included in the systematic review, comprising 1332 patients with various cancer types receiving (neo-) adjuvant chemo-, radio-, and/or hormone therapy. Exercise induced beneficial changes in (V) over dotO(2)max compared to usual care (effect size = 0.46, 95% Confidence Interval = 0.23-0.69). Longer session duration (P = 0.020), and weekly duration (P = 0.010), larger weekly volume (P < 0.001), and shorter intervention duration (P = 0.005) were significantly associated with more beneficial changes in (V) over dot O(2)max. No differences in effects between subgroups with respect to frequency and intensity were found. In conclusion, exercise has beneficial effects on (V) over dotO(2)max in patients with cancer undergoing (neo-) adjuvant treatment. As interventions with larger exercise volumes and longer session durations resulted in larger beneficial changes in (V) over dot O(2)max, exercise frequency, intensity, and duration should be considered carefully for sufficient exercise volume to induce changes in (V) over dot O(2)max for this patient group.

Keywords
aerobic exercise training, cardiorespiratory fitness, FITT factors, meta-synthesis, RCT
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:uu:diva-393758 (URN)10.1111/sms.13442 (DOI)000482146700001 ()31034665 (PubMedID)
Available from: 2019-09-27 Created: 2019-09-27 Last updated: 2019-09-27Bibliographically approved
Daskalakis, K., Norlén, O., Karakatsanis, A., Hellman, P., Larsson, R., Nygren, P. & Stålberg, P. (2018). Ex Vivo Activity of Cytotoxic Drugs and Targeted Agents in Small Intestinal Neuroendocrine Tumors. Paper presented at 15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN. Neuroendocrinology, 106(Supplement: 1), 189-189
Open this publication in new window or tab >>Ex Vivo Activity of Cytotoxic Drugs and Targeted Agents in Small Intestinal Neuroendocrine Tumors
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2018 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 189-189Article in journal, Meeting abstract (Other academic) Published
Keywords
ex vivo activity, cytotoxic drugs, targeted agents, small intestinal neuroendocrine tumors
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-354378 (URN)10.1159/000487699 (DOI)000427285300187 ()
Conference
15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN
Note

Meeting Abstract: H06

Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
Daskalakis, K., Norlén, O., Karakatsanis, A., Hellman, P., Larsson, R., Nygren, P. & Stålberg, P. (2018). Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors. Endocrine-Related Cancer, 25(4), 471-480
Open this publication in new window or tab >>Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors
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2018 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 25, no 4, p. 471-480Article in journal (Refereed) Published
Abstract [en]

Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs 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 clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinum, gemcitabine and doxorubicin compared with CRC. For several of the targeted kinase inhibitors, SI-NET was among the most sensitive solid tumor types. CLL and ovarian cancer were generally the most sensitive tumor types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. 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. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinicopathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy.

Keywords
ex vivo activity, cytotoxic drugs, targeted agents, small intestinal neuroendocrine tumor
National Category
Cancer and Oncology Surgery
Identifiers
urn:nbn:se:uu:diva-354255 (URN)10.1530/ERC-17-0404 (DOI)000430730300013 ()29440231 (PubMedID)
Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A. H., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

National Category
Cancer and Oncology Urology and Nephrology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-325565 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2020-01-08Bibliographically approved
Kashif, M., Andersson, C., Mansoori, S., Larsson, R., Nygren, P. & Gustafsson, M. G. (2017). Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism. OncoTarget, 8(61), 103952-103967
Open this publication in new window or tab >>Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 61, p. 103952-103967Article in journal (Refereed) Published
Abstract [en]

We analyzed survival effects for 15 different pairs of clinically relevant anticancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair. COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy (TM) II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of significant effect per cell line. In conclusion, the integrated Bliss and Loewe interaction analysis based on non-parametric statistics may provide more robust interaction analyses and reveal complex patterns of synergy and antagonism.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2017
Keywords
synergy analysis, combinations, iso-genic, COMBIA, R package
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-345218 (URN)10.18632/oncotarget.21895 (DOI)000419562500095 ()29262612 (PubMedID)
Available from: 2018-03-09 Created: 2018-03-09 Last updated: 2018-03-09Bibliographically approved
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