1. |
- Abdollahi, Maryam, et al.
(author)
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Anti-tumor effect of berberine on chronic lymphocytic leukemia cells
- 2022
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In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 39:12
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Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia (CLL) is a blood malignancy that is characterized by remarkable expression of CD69 and Ki67 in CLL cells. Elevated levels of Cleaved-Poly (ADP-ribose) polymerase-1 (PARP1) and microRNA-155 (MiR-155) are related to poor prognosis of disease. Berberine as a natural isoquinoline alkaloid, has shown an anti-tumor potential in tumor cells. The objective of present study was to explore some aspects of molecular mechanisms of berberine effect in CLL cells. To analyze the expression of CD69 and Ki67 using flow cytometry, 16 peripheral blood samples and seven bone marrow aspirates were collected from CLL patients. Isolated peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) were treated with 25 mu M of berberine for 24 h. The level of miR-155 expression was subsequently evaluated by real-time PCR. Furthermore, western blot was used for assessment of cleaved PARP1. Our results demonstrated a significant reduction in CD69 and Ki67 expression on CD19(+) cells when the cells were treated by berberine. Interestingly, the expression level of miR-155 was reduced after berberine treatment in compare to the control group. Furthermore, western blotting revealed an increased level of cleaved PARP1 in dose-dependently manner in CLL cells. The results confirmed the anti-tumor impact of berberine on CLL cells through reducing CD69, Ki67, and miR-155 expression and increasing cleaved PARP1 may be considered as an option for future clinical studies.
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2. |
- Afram, Gabriel, et al.
(author)
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Reduced intensity conditioning increases risk of severe cGVHD : identification of risk factors for cGVHD in a multicenter setting
- 2018
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:6
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Journal article (peer-reviewed)abstract
- Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
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3. |
- Ahlqvist-Rastad, Jane, et al.
(author)
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Erythropoietin therapy and cancer related anaemia : updated Swedish recommendations
- 2007
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:3, s. 267-272
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Journal article (peer-reviewed)abstract
- Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.
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4. |
- Albertsson, Maria, et al.
(author)
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Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer
- 2007
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:4, s. 407-412
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Journal article (peer-reviewed)abstract
- BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
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5. |
- Ali, Abir Salwa, et al.
(author)
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Intravenous versus oral etoposide : efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)
- 2018
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In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 35:4
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Journal article (peer-reviewed)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.
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6. |
- Ambring, Anneli, 1964, et al.
(author)
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Treatment with sorafenib and sunitinib in renal cell cancer: a Swedish register-based study.
- 2013
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In: Medical oncology (Northwood, London, England). - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:1
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Journal article (peer-reviewed)abstract
- Sorafenib and sunitinib are used for renal cell carcinoma (RCC). The objective was to study the treatment duration and time to death in Swedish RCC patients on sorafenib or sunitinib as first-line or monotherapy or as sequential therapy. Patients with an RCC diagnosis were identified in the Swedish Cancer Register. Information on treatment with sorafenib and sunitinib was collected from the Swedish Prescribed Drug Register, and time of death from the Cause of Death Register. Outcome measures were duration of treatment and time to death on sorafenib or sunitinib as first-line or monotherapy and sequential therapy (sorafenib-sunitinib versus sunitinib-sorafenib). Poisson regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). No difference was observed for sorafenib (n=123 patients) versus sunitinib (n=261 patients) in treatment duration (HR 1.00; CI 0.80-1.24) or risk for death (HR 1.30; CI 0.91-1.85) when used as first-line or monotherapy. The same applied for sequential therapy with sorafenib-sunitinib (n=43 patients) versus sunitinib-sorafenib (n=54 patients), HR 1.47 (CI 0.71-3.02) and HR 2.01 (CI 0.86-4.68), respectively. There was a difference between the two treatments in how the duration of first-line treatment influenced the duration of second-line treatment and time to death, in favor of starting with sorafenib. In conclusion, no difference was detected between sorafenib and sunitinib in the duration of treatment or time to death when used as first-line or monotherapy. The impact of the duration of first-line treatment differed between the two sequences, and the results indicated that sorafenib as first-line treatment is a favorable choice.
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7. |
- Amptoulach, Sousana, et al.
(author)
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Expression of caspase-3 predicts prognosis in advanced noncardia gastric cancer
- 2015
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 32:1, s. 416-416
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Journal article (peer-reviewed)abstract
- There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but also of decreased apoptosis. Caspase-3 is a member of interleukin-1 beta-converting enzyme which is involved in the induction of apoptosis. Data on the expression of caspase-3 in patients with gastric cancer and its association with patient outcome are somewhat contradictory. We aimed to investigate the potential relation of the expression of caspase-3 protein with response to therapy and overall survival in patients with advanced noncardia gastric cancer. Tumor tissue samples collected from 359 consecutive patients with gastric cancer stage IV were retrospectively analyzed for the expression of caspase-3 in the primary tumor. The DNA apoptotic index assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method. All patients were followed up until death. Caspase-3 was expressed in 43.5 % of tumors. Caspase-3 expression compared to no expression was related with a higher DNA apoptotic index (p < 0.05). In multivariate analysis, tumor expression of caspase-3 was found to be an independent predictor of poor treatment response and survival (p < 0.05). Expression of caspase-3 in advanced gastric cancer is a predictor of poor response to treatment and survival. Further studies are needed to fully elucidate the prognostic value of caspase-3 expression in these patients.
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8. |
- Andersson, Ulrika, et al.
(author)
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Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation
- 2002
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In: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:1, s. 1-9
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Journal article (peer-reviewed)abstract
- The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.
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9. |
- Bastani, Peivand, et al.
(author)
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Health-related quality of life after chemotherapy cycle in breast cancer in Iran
- 2011
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 28:S1, s. 70-74
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Journal article (peer-reviewed)abstract
- Abstract in Undetermined The aim of this study was to compare the differences between the level of whole quality of life and its subscales after receiving two common treatment of breast cancer in women with early stage of breast cancer. A double-blinded cohort study was done in 100 breast cancer patients with node positive that used fluorouracil, doxorubicin, cyclophosphamide (FAC) and docetaxel, doxorubicin and cyclophosphamide (TAC) regimen as adjuvant therapy. Patients were followed for 4 months since the end of chemotherapy. Health-related quality of life was assessed using questionnaire (QLQ-C30) from European Organization for Research and Treatment of Cancer (EORTC). Independent t-test analysis was used at the significant level of 0.05 for analyzing the results. The mean of age was 48.49 +/- 10.63 in these patients. QoL scores were 64 and 68 in TAC and FAC groups, respectively (P < 0.001). After 4 months, patients in TAC and FAC groups experienced 11.45 and 7.14 units of improvement in QoL scores, respectively (P = 0.02). Although, TAC had a more negative impact on QoL during chemotherapy, it created a higher improvement than FAC during 4 months since the end of treatment. These effects on quality of life should be considered in making decision for providing and financing cancer treatments in Iran.
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10. |
- Bergfelt, Emma, et al.
(author)
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Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia : a Swedish registry-based study
- 2015
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
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Journal article (peer-reviewed)abstract
- The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.
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11. |
- Berglund, Åke, et al.
(author)
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An explorative randomised phase II study of sequential chemotherapy in advanced upper gastrointestinal cancer
- 2010
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 27:1, s. 65-72
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Journal article (peer-reviewed)abstract
- The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric (GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m2 docetaxel or 180 mg/m2 irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were reasonably well tolerated. Grade 3–4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and appears active in advanced UGIA.
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12. |
- Birgegård, Gunnar, 1944-, et al.
(author)
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Evaluation of beta globin mRNA as an early marker of haemoglobin response to epoetin treatment
- 2007
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:3, s. 318-322
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Journal article (peer-reviewed)abstract
- Approximately 60% of anaemic cancer patients respond to epoetin treatment. An early marker of response would be valuable in order to avoid ineffective treatment. We have previously shown that beta globin mRNA increases rapidly after epoetin beta treatment of healthy controls. In the present study we have evaluated whether a change of this marker during the first 2 weeks of epoetin treatment could predict later Hb response in anaemic cancer patients. Twenty cancer patients with Hb <11 g/dl received epoetin beta (NeoRecormon®) 10,000 IU three times weekly during 6 weeks. Hb, reticulocytes and β-globin mRNA were followed. The latter was measured quantitatively using PCR via the 5′ nuclease assay. Eleven patients responded with a Hb increase of >1 g/dl, nine were nonresponders. All responders increased in β-globin mRNA within 2 weeks, mean 7.7× base-line. With a cut-off of an increase of 3× base-line value, we obtained a specificity of 45% and a sensitivity of 91% for the prediction of a later increase of Hb >1 g/dl. With a cut-off of 4× base-line, the specificity increased to 66%, but the sensitivity decreased to 82%. Beta globin mRNA increases before Hb in all responding patients. However, some non-responding patients also show an increase, and there is a trade-off between specificity and sensitivity as the cut-off level is set at different levels. Compared to reticulocyte count, β-globin mRNA is more reliable in the individual patient, but the clinical usefulness of the assay needs to be evaluated in further studies.
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13. |
- Blacker, Christopher, et al.
(author)
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Primary evaluation of an air-cooling device to reduce oral mucositis : a pilot study in healthy volunteers
- 2020
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In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 37:12
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Journal article (peer-reviewed)abstract
- Oral mucositis is a common side effect of chemo and radiotherapy causing painful ulcers in the oral mucosa. One of the preventive treatments recommended in international guidelines is oral cryotherapy (OC). Randomized clinical trials on OC have used ice and ice-chips to cool the mouth, but this cooling method can be difficult for the patients to tolerate. Studies have shown that OC with ice for a period of 60 min reduces the oral temperature by 12.9 degrees C. The aim of this pilot study was to evaluate the temperature reduction and tolerability of OC using an intra-oral air-cooling (IOAC) device in healthy volunteers. Twelve healthy volunteers, mean age 35.4 years, were included in the study. They were treated with OC using the IOAC device for 60 min. Measurements of temperature were obtained at baseline, 5 and 60 min using a FLIR (R) C2 camera. After the OC session, tolerability and adverse events were documented using a questionnaire. All participants were able to use the device for 60 min. The overall temperature reduction after 5 min of OC was 10.7 degrees C (p < 0.01) and after 60 min 14.5 degrees C (p < 0.01). The most common adverse events were bad fit of the mouthpiece (n = 6), hypersalivation (n = 6), and difficulties swallowing (n = 5). The oral device reduced the temperature of the oral mucosa as much as treatment with ice with tolerable adverse events. The mouthpiece will be remodeled to improve tolerability before further studies are conducted.
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14. |
- Blacker, C, et al.
(author)
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Randomized cross-over study investigating the tolerability and side effects of an intra-oral air-cooling device compared to ice in healthy volunteers
- 2023
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In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 40
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Journal article (peer-reviewed)abstract
- Oral cryotherapy (OC) is a common preventive treatment of oral mucositis (OM) and is recommended in international guidelines. Ice and air OC have previously been shown to result in temperature reductions of 8.1-12.9 degrees C, and 14.5 degrees C, respectively, in healthy volunteers. However, no direct comparison between these two modalities has been performed. The primary aim was to investigate the tolerability and side effects of air OC using an intra-oral air-cooling (IOAC) device compared with ice OC. The secondary aim was to evaluate the temperature reduction in the mouth for the two respective methods. Cross-over study with randomization to order of treatment, in 15 healthy volunteers. We evaluated the self-reported intensity, frequency, and discomfort for 13 pre-defined side effects used in previous studies. All participants were able to complete both OC sessions, although one participant required reduced airflow in the air OC arm. The subjects reported more discomfort from being cold, having sensitive teeth, and numbness in the ice OC group, while they reported more discomfort from swallowing when subjected to air OC. No significant difference in the median temperature reduction was detected in the two modalities, except for the dorsal posterior part of the tongue where temperature reduction was larger in the ice OC group. We found that oral cooling using a new IOAC device was tolerated and seems to be safe in healthy volunteers.
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15. |
- Bukkuri, Anuraag, et al.
(author)
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Modeling cancer’s ecological and evolutionary dynamics
- 2023
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 40:4
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Journal article (peer-reviewed)abstract
- In this didactic paper, we present a theoretical modeling framework, called the G-function, that integrates both the ecology and evolution of cancer to understand oncogenesis. The G-function has been used in evolutionary ecology, but has not been widely applied to problems in cancer. Here, we build the G-function framework from fundamental Darwinian principles and discuss how cancer can be seen through the lens of ecology, evolution, and game theory. We begin with a simple model of cancer growth and add on components of cancer cell competition and drug resistance. To aid in exploration of eco-evolutionary modeling with this approach, we also present a user-friendly software tool. By the end of this paper, we hope that readers will be able to construct basic G function models and grasp the usefulness of the framework to understand the games cancer plays in a biologically mechanistic fashion.
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16. |
- Cavalli-Björkman, Nina, et al.
(author)
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Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia
- 2002
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In: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:4, s. 277-80
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Journal article (peer-reviewed)abstract
- Alemtuzumab (Campath-1H) is a humanized CD52 monoclonal antibody that targets normal as well as malignant B- and T-lymphocytes. Alemtuzumab has significant antitumor activity in chronic lymphocytic leukemia (B-CLL) but also induces immunosuppression. We describe a case of fatal adenovirus infection in a heavily pretreated patient with fludarabine-refractory B-CLL receiving alemtuzumab therapy, drawing attention to the fact that also viruses other than cytomegalovirus (CMV) and herpes simplex (HSV) need to be considered in B-CLL patients with fever of unknown origin while on alemtuzumab treatment.
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17. |
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18. |
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19. |
- Drottz-Sjöberg, Britt-Marie, et al.
(author)
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Psychological reactions to cancer risks after the Chernobyl accident
- 1987
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In: Medical Oncology. - : Humana Press. - 1559-131X .- 1357-0560. ; 4:3-4, s. 259-271
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Journal article (peer-reviewed)abstract
- This is a report on an investigation of people's reactions to the Chernobyl accident. Interviews and, mail surveys were conducted in July-September 1986 with pregnant women, parents of newborn children, farmers, adolescents and men who were not parents, in various areas of Sweden, differing as to the amount of Chernobyl fallout they had received. The accident had probably doubled the number of people who were negative to nuclear power in the most affected area. Radiation risks were highly salient in most groups. Areas differed in the expected direction, people in the more, exposed areas being more concerned. Women were more worried and more negative to nuclear power than men while adolescents appeared to be the group least affected by the accident. Farmers were also strongly opposed to nuclear power and concerned about its risks. Nuclear attitude could be well accounted for by attitude statements and rated basic life values. It was quite stable over a 1 month period.
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20. |
- Du, J., et al.
(author)
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Aberrant elevated microRNA-146a in dendritic cells (DC) induced by human pancreatic cancer cell line BxPC-3-conditioned medium inhibits DC maturation and activation
- 2012
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 29:4, s. 2814-2823
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Journal article (peer-reviewed)abstract
- It has been shown that the function of dendritic cell (DC) is suppressed in pancreatic cancer patients; however, the detailed mechanism involved in it remains unclear. Here, we used medium conditioned by a highly metastatic human pancreatic cancer cell line BxPC-3 [BxPC-3-conditioned medium (BxCM)] to culture human CD14 + monocyte-derived DCs in vitro. Both DC differentiation and antigen presentation function were inhibited by BxCM. The microRNA-146a (miRNA-146a) expression is aberrantly up-regulated in BxCM-treated DCs. In addition, inhibition of aberrant miRNA-146a expression partly rescues the BxCM-induced defects in differentiation and function of DCs, which may be through regulation of Smad4 expression. Taken together, our findings indicate that aberrant miRNA-146a expression is one of main factors responsible for inhibition of DC maturation and antigen presentation function, and this inhibitory effect on DCs may be due to the repression of Smad4 mediated signal pathway by BxCM.
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21. |
- Falk, Peter, 1962, et al.
(author)
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Role of matrix metalloproteinases in tumour invasion: immunohistochemistry of peritoneum from peritoneal carcinomatosis
- 2018
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:5
-
Journal article (peer-reviewed)abstract
- Colorectal cancer is one of the most common forms of cancer. Spread of tumour to the peritoneal cavity may lead to seeding of cancer cells that adhere to and invade the peritoneal membrane causing peritoneal carcinomatosis. Matrix metalloproteinases (MMPs) play an essential role in cancer cell invasion and dissemination. The aim of this study was to evaluate the morphology and presence of matrix metalloproteinases in peritoneal carcinomatosis. Biopsy samples of the parietal peritoneum were taken from patients undergoing cytoreductive surgery for peritoneal carcinomatosis. The samples were fixed in formalin, dehydrated and embedded in paraffin prior to cutting into 4-mu m slices. Staining with haematoxylin/eosin was used for morphology studies, and MMP-1, MMP-2 and TIMP-1 levels were evaluated using immunohistochemistry and light microscopy. The microscopically tumour-free areas of the peritoneal membrane were thin compared to the peripheral invasion zone and the areas invaded by tumour. Peritoneum invaded by tumour was richly vascularised and contained inflammatory cells. MMP-1 was expressed in tumour-free peritoneum and in the invasion zone between tumour and peritoneal tissue, but not in tumour-invaded areas. MMP-2 and TIMP-1 were mostly expressed in the proximity of blood vessels and inflammatory cells in tumour-invaded areas, but was not seen in tumour-free areas. MMPs play an important role in the process of cancer cell invasion of the peritoneum in peritoneal carcinomatosis. The peripheral zone of the tumour appears to be of importance for tumour invasion.
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22. |
- Fjällskog, Marie-Louise, et al.
(author)
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Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors
- 2003
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In: Medical Oncology. - 1357-0560 .- 1559-131X. ; 20:1, s. 59-67
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Journal article (peer-reviewed)abstract
- Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst2 and sst4 stained positive in 90% and sst1 in 70% of the tumor tissues, whereas sst3 and sst5 stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst2 and sst4 (80%), moderate for sst1 (40%), and low for sst3 and sst5 (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst2 and sst4 were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.
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23. |
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24. |
- Fransson, Susanne, 1975, et al.
(author)
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High level of p37δ-mRNA relative to p110δ-mRNA in neuroblastoma tumors correlates with poor patient survival
- 2013
-
In: Medical Oncology. - : Springer Science+Business Media B.V.. - 1357-0560 .- 1559-131X. ; 30:4
-
Journal article (peer-reviewed)abstract
- Alterations in the PI3K/Akt pathway, a pathway that promotes proliferation and oncogenic transformation, are common in various cancers. In neuroblastoma, activation of Akt is correlated with aggressive disease although mutations in genes of this pathway are rare. Previous findings include a few mutations in PIK3CD, the gene encoding PI3K catalytic subunit delta, p110delta. We recently reported that an alternatively spliced form of p110delta, called p37delta, had cell proliferative properties and was over-expressed in ovarian and colorectal tumors. Here, we investigated p37delta in neuroblastoma primary tumors of different stages using qPCR (TaqMan) for gene expression analysis (46 samples) and Western blot for protein analysis (22 samples). Elevated levels of both p37delta-mRNA and p110delta-mRNA were detected in metastasizing neuroblastoma tumors compared to normal adrenal gland (P<0.05), and higher expression of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma non-survivor patients compared to survivors (P<0.01). p37delta-Protein levels but not p110delta levels correlated with increased pAKT(T308) and pERK levels. The p37delta-mRNA levels did not correlate with the protein levels, indicating major regulation at the translational/protein level. Deregulation of signaling pathways is a hallmark of cancer development. Here, we show that p37delta, a kinase-dead isoform of the PI3K catalytic subunit p110delta, is over-expressed in neuroblastoma tumors, and that it correlates with the activation of both PI3K/Akt- and RAS-signaling pathways.
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25. |
- Grund, Sofia, et al.
(author)
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The autocrine motility factor receptor is overexpressed on the surface of B cells in Binet C chronic lymphocytic leukemia.
- 2011
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 28:4, s. 1542-8
-
Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a clinical spectrum reaching from discrete lymphocytosis to extensive enlargement of lymph nodes, spleen and liver, and bone marrow failure. The aim of this study was to identify genes that differentiate between patients with disease stage A vs. C according to Binet in order to better understand the disease. To achieve this, we performed DNA microarray analysis on B cells from CLL patients with stage A and C according to Binet and matched controls. Between CLL patients and controls, there were 1,528 differentially expressed genes and 360 genes were differentially expressed between Binet A and C patients. Due to the sheer number of regulated genes, we focused on the autocrine motility factor receptor (AMFR). AMFR has not previously been investigated in hematological disorders, but high expression of AMFR correlates with a more advanced stage and invasive potential in several human tumors. AMFR mRNA expression was higher in Binet A compared with Binet C patients (P=0.0053) and healthy controls (P=0.0051). Total AMFR protein was higher in Binet A patients compared to Binet C as analyzed by intracellular flow cytometry. However, AMFR exist both in the ER involved in protein degradation and on the cell surface involved in metastasis and cell motility. Cell surface AMFR was increased in Binet C compared with Binet A+B (P=0.016). In conclusion, the mRNA levels reflect the total amount of AMFR, whereas cell surface expression is associated with progression in CLL.
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26. |
- Gubanski, M., et al.
(author)
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Quality of life in patients with advanced gastric cancer sequentially treated with docetaxel and irinotecan with 5-fluorouracil and folinic acid (leucovin)
- 2014
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:4, s. 906-
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Journal article (peer-reviewed)abstract
- With a median overall survival of only 9-13 months in patients with advanced gastric cancer (GC), the quality of life (QoL) during the palliative treatment remains a key issue. Furthermore, when combinations of two or three drugs are used, the impact on QoL should be carefully evaluated. This was studied within the GATAC trial in patients sequentially treated with docetaxel and irinoteca n with 5-fluorouracil and leucovorin (5-Fu/ Lv). Patients with previously untreated advanced GC were randomly assigned to start with docetaxel 45 mg/m(2) (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus and 44 h infusion of 5-Fu/Lv (D1, q2 weeks). After four courses, there was a prescheduled crossover to the alternative regimen for four additional courses. QoL was measured with the EORTC QLQ-C30 questionnaire at the start of the treatment, at crossover and after completing treatment with both regimens. Eighty-one patients were randomized, and 78 patients started treatment. A total of 191 completed QoL questionnaires were collected. There were no statistically significant differences in QoL scores between the two treatment groups and no changes in mean scores during the 16 weeks of treatment. During the last 8 weeks of treatment, a significantly larger portion of patients with radiological response reported sustained or better QoL scores than those with no radiological response (82 vs. 50 %, p = 0.007). Chemotherapy in advanced GC did not affect QoL average scores. Patients with non-responding tumours reported more often a decline in the global QoL score. The concept of the pre-scheduled switch of chemotherapy regimens prior to progression should be further studied in this disease, as it appears effective, tolerable and not to negatively affect QoL.
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27. |
- Gülen, T, et al.
(author)
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Systemic mastocytosis : progressive evolution of an occult disease into fatal mast cell leukemia
- 2012
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 29:5, s. 3540-3546
-
Journal article (peer-reviewed)abstract
- Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors' knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL.
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28. |
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29. |
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30. |
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31. |
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32. |
- Hammarlund, Emma U., et al.
(author)
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The issues with tissues : the wide range of cell fate separation enables the evolution of multicellularity and cancer
- 2020
-
In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 37:7
-
Journal article (peer-reviewed)abstract
- Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.
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33. |
- Hedenus, Michael, et al.
(author)
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Intravenous iron alone resolves anemia in patients with functional iron deficiency and lymphoid malignancies undergoing chemotherapy
- 2014
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:12, s. 302-
-
Journal article (peer-reviewed)abstract
- This randomized trial evaluated ferric carboxymaltose without erythropoiesis-stimulating agents (ESA) for correction of anemia in cancer patients with functional iron deficiency. Patients on treatment for indolent lymphoid malignancies, who had anemia [hemoglobin (Hb) 8.5-10.5 g/dL] and functional iron deficiency [transferrin saturation (TSAT) <= 20 %, ferritin >30 ng/mL (women) or >40 ng/mL (men)], were randomized to ferric carboxymaltose (1,000 mg iron) or control. Primary end point was the mean change in Hb from baseline to weeks 4, 6 and 8 without transfusions or ESA. Difficulties with patient recruitment led to premature termination of the study. Seventeen patients (8 ferric carboxymaltose and 9 control) were included in the analysis. In the ferric carboxymaltose arm, mean Hb increase was significantly higher versus control at week 8 (p = 0.021). All ferric carboxymaltose- treated patients achieved an Hb increase >1 g/dL (control 6/9; p = 0.087), and mean TSAT was >20 % from week 2 onwards. No treatment-related adverse events were reported. In conclusion, ferric carboxymaltose without ESA effectively increased Hb and iron status in this small patient population.
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34. |
- Hedenus, Michael, et al.
(author)
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The role of iron supplementation during epoietin treatment for cancer-related anemia
- 2009
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 26:1, s. 105-115
-
Research review (peer-reviewed)abstract
- Cancer-related anemia is common and multifactorial in origin. Functional iron deficiency (FID) is now recognized as a cause of iron-restricted erythropoiesis and may be one of the major reasons for lack of response to treatment with Erythropoietic Stimulating Agents (ESAs). Numerous studies have shown that intravenous (IV), but not oral, iron therapy effectively provides sufficient iron for optimal erythropoiesis in anemic patients with chronic renal disease receiving ESA therapy. The use of IV iron has also been suggested in the cancer setting. Six recent studies have tested this assumption and are summarized in this review. Four formulations of IV iron are available in Europe, with different pharmacokinetics, iron bioavailability, and risk of acute adverse drug reactions. Conclusion: Limited iron stores and FID are common causes of response failure during ESA treatment in cancer patients and should be diagnosed. There is now substantial scientific support for the use of IV iron supplementation to improve response and this has been acknowledged in international and national guidelines. Prospective long-term data on the safety of IV iron in this setting are still awaited. Recommendations concerning the optimal formulation, doses, and schedule of iron supplementation to ESA treatment in cancer-related anemia are provisional awaiting data from prospective, randomized trials.
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35. |
- Holgersson, Georg, et al.
(author)
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A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer
- 2015
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
-
Journal article (peer-reviewed)abstract
- AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.
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36. |
- Holgersson, Georg, et al.
(author)
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Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer
- 2012
-
In: Medical Oncology. - : Humana Press (Springer Imprint). - 1357-0560 .- 1559-131X. ; 29:5, s. 3176-3182
-
Journal article (peer-reviewed)abstract
- There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (andgt; 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb andlt; 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC andgt; 9.0 x 10(9)/L and andlt; 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p andlt; 0.0001). For Plt andgt; 350 x 10(9)/L and andlt; 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p andlt; 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p andlt; 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.
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37. |
- Holgersson, Georg, et al.
(author)
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The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer
- 2013
-
In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
-
Journal article (peer-reviewed)abstract
- The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected to curatively intended irradiation (andgt;= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Patients who did not have a histopathological diagnosis date and/or death date/last follow-up date as well as patients being surgically treated were excluded from the study (n = 592). Thus, 695 patients were included in the present study. Patients who received hyperfractionated radiotherapy (HR) had a higher local control rate compared with patients receiving conventional fractionation (CF) (38 vs. 49 % local relapse). The difference in survival between the two radiotherapy regimens was statistically significant in a univariate Cox analysis (p = 0.023) in favor of HR. This significance was, however, not retained in a multivariate Cox analysis (p = 0.56). Thus, the possible beneficial effects of hyperfractionation are still unclear and need to be further investigated in well-controlled prospective clinical trials, preferably including systemic treatment with novel drugs.
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38. |
- Hulegardh, E., et al.
(author)
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Outcome after HSCT in Philadelphia chromosome positive acute lymphoblastic leukemia in Sweden : a population-based study
- 2014
-
In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:8, s. 66-
-
Journal article (peer-reviewed)abstract
- Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients <40 years 70 (50-90) % and for patients >= 40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients <40 years 10 (2-28) % compared to 25 (11-42) % for patients >= 40 years (p = 0.04). Patients with chronic graft-versus-host disease (GVHD) had a 5-year morphological relapse probability of 20 (6-40) % compared to 59 (35-77) % for patients without chronic GVHD (p = 0.03). Age >= 40 years and the absence of chronic GVHD were confirmed as independent negative prognostic factors for relapse and non-relapse mortality in a multivariate analysis although the impact of chronic GVHD was significant only in the older age cohort.
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39. |
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40. |
- Hägglund, Hans, et al.
(author)
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Analysis of V600E BRAF and D816V KIT mutations in systemic mastocytosis
- 2014
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:8, s. 123-
-
Journal article (peer-reviewed)abstract
- Most patients with systemic mastocytosis (SM) carry a D816 V KIT mutation causing a ligand-independent activation of the receptor. Down-stream of KIT is several components known to be mutated in different malignancies. RAF is among the most frequently mutated kinases, where BRAF V600E mutation occurs in most hairy cell leukemias (HCL) and half of malignant melanomas. We investigated BRAF mutations in 36 subjects with different forms of SM, but could not detect BRAF mutation in any of the cases, not even in the mast cell lineage of a patient with V600E BRAF-positive HCL. Thus, although BRAF is commonly mutated it appears not to be present in SM.
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41. |
- Jacques, Florian, et al.
(author)
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Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics
- 2022
-
In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 39:11
-
Journal article (peer-reviewed)abstract
- The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals’ unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue—normal and transformed—can also contribute the framework for exploring animal evolution.
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42. |
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43. |
- Jonsson, Andreas, 1984, et al.
(author)
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Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer.
- 2018
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In: Medical oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 35:4
-
Journal article (peer-reviewed)abstract
- Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at -80°C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9years of cryopreservation (median values 9.9 and 9.7ng/mL, respectively; p>0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1ng/mL, respectively; p<0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5ng/mL, respectively; p<0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at -80°C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.
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44. |
- Jung, Michaela, et al.
(author)
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A clinical study of metastasized rectal cancer treatment : assessing a multimodal approach
- 2014
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In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 31:3, s. 839-
-
Journal article (peer-reviewed)abstract
- Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery.
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45. |
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46. |
- Kabir, Nuzhat N., et al.
(author)
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Deregulation of protein phosphatase expression in acute myeloid leukemia
- 2013
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:2
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is a highly malignant disease of myeloid cell line. AML is the most frequent adult leukemia with inadequate treatment possibility. The protein phosphatases are critical regulators of cell signaling, and deregulation of protein phosphatases always contribute to cell transformation. Although many studies established a relationship between protein phosphatases and leukemia, little is known about the role of this group of proteins in AML. To address this issue, we initially identified the complete catalog of human protein phosphatase genes and used this catalog to study deregulation of protein phosphatases in AML. Using mRNA expression data of AML patients, we show that 11 protein phosphatases are deregulated in AML within 174 protein phosphatases. The GO enrichment study suggests that these genes are involved in multiple biological processes other than protein de-phosphorylation. Expression of DUSP10, PTPRC, and PTPRE was significantly higher than average expression in AML, and a linear combination of DUSP10, MTMR11, PTPN4, and PTPRE expressions provides important information about disease subtypes. Our results provide an overview of protein phosphatase deregulation in AML.
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47. |
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48. |
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49. |
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50. |
- Kazi, Julhash U., et al.
(author)
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Protein kinase C (PKC) as a drug target in chronic lymphocytic leukemia.
- 2013
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In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:4, s. 757-757
-
Research review (peer-reviewed)abstract
- Protein kinase C (PKC) belongs to a family of ten serine/threonine protein kinases encoded by nine genes. This family of proteins plays critical roles in signal transduction which results in cell proliferation, survival, differentiation and apoptosis. Due to differential subcellular localization and tissue distribution, each member displays distinct signaling characteristics. In this review, we have summarized the roles of PKC family members in chronic lymphocytic leukemia (CLL). CLL is a heterogeneous hematological disorder with survival ranging from months to decades. PKC isoforms are differentially expressed in CLL and play critical roles in CLL pathogenesis. Thus, isoform-specific PKC inhibitors may be an attractive option for CLL treatment.
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