| 1. |
- Adra, Jamila, et al.
(author)
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Blood biomarkers for neuroaxonal injury and astrocytic activation in chemotherapy-induced peripheral neuropathy
- 2024
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In: ACTA ONCOLOGICA. - 0284-186X .- 1651-226X. ; 63, s. 636-641
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Journal article (peer-reviewed)abstract
- Background and purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. Materials and methods: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks x 3, followed by weekly paclitaxel 80 mg/ m2 x 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. Results: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. Interpretation: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.
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| 2. |
- Andersson, Anton E, et al.
(author)
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Delta NT-proBNP predicts cardiotoxicity in HER2-positive breast cancer patients treated with trastuzumab.
- 2021
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 60:4, s. 475-481
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Journal article (peer-reviewed)abstract
- Overall survival has improved significantly in patients with human epidermal growth receptor 2 (HER2)-positive breast cancer due to the use of the monoclonal antibody trastuzumab blocking HER2. However, patients may develop trastuzumab-induced cardiotoxicity (TIC) leading to congestive heart failure. Here we assessed whether analysing NT-proBNP and assessment of electrocardiography (ECG) could detect TIC during trastuzumab therapy.One hundred thirty-six patients undergoing adjuvant, neoadjuvant or palliative chemotherapy and HER2 blockade for HER2-positive breast cancer were prospectively assessed with echocardiography, ECG and N-terminal - pro hormone B-type natriuretic peptide (NT-proBNP) testing at baseline and at 6 and 12months of trastuzumab therapy. TIC was defined as a left ventricular ejection fraction (LVEF) of less than 50% and a decline from baseline of ≥10 units.Six patients developed TIC under 12months of trastuzumab therapy (incidence 4.4%). NT-proBNP increased from 198.8±64.0pg/ml to 678.7±132.4pg/ml (p<.05) in TIC patients. With a cut-off point of 276.5pg/ml for NTproBNP and increase in NT-proBNP by 75.8pg/ml from baseline the sensitivity was 100% and the specificity 95% to detect TIC. Compared with controls, TIC patients were older (68.3±1.1years and 56.2±1.4years, respectively; p<.01), had more often diabetes mellitus (OR = 63.5, 95% CI: 5.63-915, p<.01) and atrial fibrillation (OR = 12.3; 95% CI: 1.89-74.62; p<.05) and had lower baseline LVEF (57.1±1.4% and 61.4±0.3%, respectively; p<.001). Abnormal ECGs were common in patients developing TIC.Measuring changes in NTproBNP may be used to monitor patients for TIC under trastuzumab therapy. Patients with a cardiovascular risk profile are more at risk of developing TIC.
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| 3. |
- Aurell, Carolina, et al.
(author)
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Follow-up Routines Matter for Adherence to Endocrine Therapy in the Adjuvant Setting of Breast Cancer
- 2024
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In: BREAST CANCER-BASIC AND CLINICAL RESEARCH. - 1178-2234. ; 18
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Journal article (peer-reviewed)abstract
- Background: Endocrine therapy (ET) adherence leads to increased survival in breast cancer (BC). How follow-up should be done to maximize adherence is not known. Objectives: To assess adherence to ET, factors favouring adherence to ET and effects on survival in a population-based cohort of BC patients in western Sweden. Design: This is a retrospective study. Methods: We included 358 patients operated for oestrogen receptor-positive BC and recommended 5 years of ET, in Region Halland, Sweden, year 2015 to 2016. Demographical, clinical and pathological data and use of ET were retrieved from the electronic medical records. Patients were considered adherent if taking ET for 5 years or during the full extent of the follow-up, until termination of ET due to BC relapse or death and where renewals of prescriptions of ET covered >80% of the ordinated dose. Two follow-up routines were employed, ie, routine A where patients were contacted annually by nurses and a more passive follow-up routine B where patients were only contacted by nurses at 2 years and 5 years following start of ET. Results: Medication persistence for 4 years and more was good and similar between patients initiating aromatase inhibitor (AI) and tamoxifen (75.7% and 72.0%, respectively, P = .43). More patients initiating AIs changed ET due to side effects compared with patients initiating tamoxifen (24.3% vs 9.9%, respectively, P < .0001). Endocrine therapy adherence was better for follow-up routine B than for follow-up routine A (hazard ratio [HR] = 2.71 [1.44-5.09], P = .0027). Conclusions: Adherence to ET in BC is high in Western Sweden. Less regular nurse-initiated contacts between BC patients and nursesled surprisingly to a better adherence than a more regular nurse-initiated contact.
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| 4. |
- Bienvenu, E., et al.
(author)
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Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection-A Prospective Study in HIV Positive and HIV Negative Rwandan Women
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:23
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Journal article (peer-reviewed)abstract
- Simple Summary Cervical cancer is the predominant cause of female cancer deaths in Sub-Saharan Africa. Chronic infection of the uterine cervix by the human papillomavirus (HPV) is the most important factor for the development of cervical cancer. HPV screening may be used to screen out women at risk of cervical cancer; however, the majority of HPV infections will eventually heal, and at present, there are no screening methods to detect which HPV infections that will become chronic. In the present study, we followed HIV-negative and HIV-positive Rwandan women with cervical HPV infections for two years with repeated samplings from the uterine cervix. We identified protein biomarkers that correlate with the potential risk for women to develop cervical cancer. By including the identified biomarkers in cervical screening programs, we are able, potentially, to identify those women with cervical HPV infections, who should be carefully monitored in the future. Background: Effects on the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic were investigated. Moreover, biomarker panels that could identify cervical risk lesions were assessed. Methods: Cytology, HPV screening and proteomics were performed on cervical samples from Rwandan HIV+ and HIV- women at baseline, at 9 months, at 18 months and at 24 months. Biological pathways were identified using the String database. Results: The most significantly affected pathway when an incident HR-HPV infection occurred was neutrophil degranulation, and vesicle-mediated transport was the most significantly affected pathway when an HR-HPV infection was cleared; protein insertion into membrane in chronic HR-HPV lesions and in lesions where HR-HPVs were cleared were compared; and cellular catabolic process in high-grade lesions was compared to that in negative lesions. A four-biomarker panel (EIF1; BLOC1S5; LIMCH1; SGTA) was identified, which was able to distinguish chronic HR-HPV lesions from cleared HR-HPV/negative lesions (sensitivity 100% and specificity 91%). Another four-biomarker panel (ERH; IGKV2-30; TMEM97; DNAJA4) was identified, which was able to distinguish high-grade lesions from low-grade/negative lesions (sensitivity 100% and specificity 81%). Conclusions: We have identified the biological pathways triggered in HR-HPV infection, when HR-HPV becomes chronic and when cervical risk lesions develop. Moreover, we have identified potential biomarkers that may help to identify women with cervical risk lesions.
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| 5. |
- Dafar, Amal, et al.
(author)
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Langerhans Cells, T Cells, and B Cells in Oral Lichen Planus and Oral Leukoplakia
- 2022
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In: International Journal of Dentistry. - : Hindawi Limited. - 1687-8728 .- 1687-8736. ; 2022
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Journal article (peer-reviewed)abstract
- Although oral lichen planus (OLP) and oral leukoplakia (LPL) have different pathogenetic profiles, both may involve chronic inflammation. The aim of this observational study was to evaluate the inflammatory cell profiles of OLP and LPL. The inflammatory cell infiltrates in patients with OLP and LPL were analyzed for the presence of Langerhans cells (LCs; CD1a), T cells (CD3), and B cells (CD20), as well as for the proliferation marker Ki-67. Biopsied specimens from patients with OLP (N = 14) and LPL without dysplasia (N = 13) were immunohistochemically stained with antibodies directed against CD1a, CD3, CD20, and Ki-67, followed by quantitative analyses. A significant increase in the number of CD3+ cells and CD20+ cells was found in the submucosa of OLP, as compared to LPL (p<0.01). Likewise, the number of CD3+ cells was significantly higher in the epithelium of OLP than of LPL (p<0.05). No differences were found in the expression of Ki-67 and the number of CD1a+ cells between the two groups. Although an immune response is elicited in both conditions, there are differences at the cellular level between OLP and LPL. A more robust immune activation involving T cells and B cells is seen in OLP. The role of B cells in OLP needs to be further elucidated. Although the number of B cells in LPL is low, their role in the inflammatory response cannot be ruled out.
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| 6. |
- dos Santos, W. P., et al.
(author)
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Morphology, Volume, and Density Characteristics of the Parotid Glands before and after Chemoradiation Therapy in Patients with Head and Neck Tumors
- 2020
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In: International Journal of Dentistry. - : Hindawi Limited. - 1687-8728 .- 1687-8736. ; 2020
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Journal article (peer-reviewed)abstract
- The multimodal approach for patients with head and neck cancer (HNC) includes treatment with chemoradiation therapy (CRT). A common concern regarding CRT side effects is the occurrence of structural and physiological alterations of the salivary glands due to exposure to ionizing radiation. The aim of this study is to examine the morphology, volume, and density of the parotid glands before and after CRT in HNC patients. A total of 49 HNC patients treated exclusively with CRT were included in the study. Ninety-eight parotid glands were evaluated before and after treatment by using contrast-enhanced computed tomography (CECT). Shapiro-Wilk test was performed, and the variables (pre-CRT and post-CRT) presented normal distribution. Pearson's coefficient was used to assess the correlation between volume and density. CRT resulted in a significant decrease in the mean volume of the parotid glands (i.e., original volume reduced by 20.5%; P<0.0001). CRT induced a 30.0% (7 Hounsfield units) increase in density of the right parotid gland and a 24.9% (8 Hounsfield units) increase in density of the left parotid gland (P=0.0198 and P=0.0079, respectively). Changes in morphology and spatial configuration, increased density, and substantial loss of volume of the parotid glands were observed after CRT. There was also a difference in density (P=0.003) in the right-side parotid glands in comparison between xerostomic and nonxerostomic groups of patients. These facts lead to the need for a personalized CRT planning in order to minimize oral complications related to the treatment.
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| 7. |
- Ganesh, Divya, et al.
(author)
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EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation
- 2023
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In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 43:4, s. 1533-1542
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Journal article (peer-reviewed)abstract
- Background/Aim: The EZH2 complex is involved in cellular proliferation and modulates the immune response in cancer. Less is known about the importance of EZH2 in precancerous lesions such as oral leukoplakia (OL). The aim of the study was to explore the association between EZH2 expression, immune activation, and cancer transformation in OL. Patients and Methods: Analyses were retrospectively performed on nine OL cases that had undergone transformation to oral squamous cell carcinoma (OSCC; OL-ca) and nine that had not undergone transformation (OL-non). EZH2-expressing cells, CD3+ and CD8+ T cells, and CD1a+ Langerhans cells were visualized with immunohistofluorescence and counted. Results: A moderate positive correlation between CD3-and EZH2-expressing and CD8-and EZH2-expressing cells in the epithelium was found (r=0.57, p=0.01; r=0.59, p=0.01). The number of EZH2-expressing cells in the epithelium of OL-ca was significantly higher compared to OL-non (p=0.0002). Cancer - free survival rates differed significantly between patients with EZH2high compared to EZH2low expression (p=0.001). EZH2high expression in OL epithelium was associated with a 13-fold higher risk for developing OSCC (HR=12.8). Conclusion: EZH2 expression in oral epithelium predicts OSCC transformation of OL and correlates with the level of T-cell infiltration.
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| 8. |
- Giglio, Daniel, 1977, et al.
(author)
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Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome.
- 2020
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In: Case reports in oncology. - : S. Karger AG. - 1662-6575. ; 13:3, s. 1252-1257
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Journal article (peer-reviewed)abstract
- We here report on a 74-year-old man diagnosed with a pT3cN0 BRAF-mutated and mismatch repair-deficient adenocarcinoma in the colon ascendens and 3 liver metastases. After hemicolectomy, the patient received treatment with the PD-1 inhibitor pembrolizumab. Three weeks later (on day 22), laboratory tests showed leukocytosis and an increase in transaminases; immune checkpoint inhibitor (ICI)-induced hepatitis was suspected and prednisolone therapy was initiated. On day 29, the patient was acutely hospitalized due to dyspnea, somnolence and walking difficulties. Dysarthria, hoarseness, muscle pain and weakness had developed and the dose of prednisolone was increased. Serum levels of lactate dehydrogenase, creatine kinase and myoglobin were increased and ICI-induced myositis was suspected. Antibodies against acetylcholine receptor and titin were present, indicating myasthenia gravis. Eventually, bulbar myopathy developed, including dysarthria and dysphagia, and the patient could no longer attain saturation without oxygen. The patient was transferred to the intensive care unit, intubated and given methylprednisolone, intravenous immunoglobulins and infliximab. The patient developed carbon dioxide retention and died on day 39. Microscopical examination of the intercostal musculature, diaphragm, cervical musculature and tongue showed inflammatory infiltration and fibrosis consistent with a pronounced myositis. In the liver, microscopical examination did not show metastases from colorectal cancer but instead a hepatocellular cancer. The cause of death was determined as respiratory insufficiency due to polymyositis. In conclusion, ICIs may induce myositis combined with neurological immune-related adverse events. In patients developing muscle weakness and pain under ICI therapy, myositis should be suspected.
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| 9. |
- Inci, Kamuran, et al.
(author)
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Palliative resection of the primary tumour improves survival in incurable metastatic colorectal cancer.
- 2023
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In: ANZ journal of surgery. - 1445-2197. ; 93:11, s. 2680-2685
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Journal article (peer-reviewed)abstract
- Studies show conflicting results on whether primary tumour resection (PTR) in metastatic colorectal cancer (mCRC) prolongs survival. The aim of this study was to analyse prognostic factors and the effects of PTR on overall survival (OS) in mCRC patients.In this population-based cohort study, factors associated with PTR and OS were assessed in 188 mCRC patients with mCRC treated with palliative chemotherapy between 2008 and 2019. The Chi-square test and Mann-Whitney U-test were used to assess factors associated with PTR. The log-rank test was used to compare Kaplan-Meier estimates for OS. Cox regression was used to identify factors predicting OS.Patients undergoing PTR had significantly better performance status, fewer metastatic sites, lower CEA levels, and more often had left-sided CRC than patients not undergoing PTR. OS was longer in palliative mCRC patients undergoing PTR (P<0.01) and PTR was an independent variable in the Cox regression analysis (P<0.05). Median OS was 22.9±1.9months for the PTR group and 14.5±1.5months for the non-operated group. Poor performance status and liver metastases were significantly associated with poor prognosis.This study shows that PTR had a positive effect on OS and may be considered in patients suitable for surgery. PTR was offered to palliative mCRC patients with prognostic factors associated with better prognosis.
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| 10. |
- Inci, Kamuran, et al.
(author)
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Targeted Therapy in the Palliative Setting of Colorectal Cancer-Survival and Medical Costs
- 2023
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In: Cancers. - 2072-6694. ; 15:11
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Journal article (peer-reviewed)abstract
- (1) Background: Targeted therapy is used alone or together with chemotherapy in metastatic colorectal cancer. The aim of this study was to assess overall survival and medical costs in a cohort of patients with metastatic colorectal cancer. (2) Methods: Demographic and clinical characteristics of 337 patients and pathological data of colorectal tumors were retrospectively collected in this population-based study. The overall survival and medical costs for patients receiving chemotherapy plus targeted therapy were compared with those for patients receiving chemotherapy only. (3) Results: Patients administered chemotherapy plus targeted therapy were less frail and had more often RAS wild-type tumors but had higher CEA levels than patients receiving chemotherapy only. No prolonged overall survival could be observed in patients receiving palliative targeted therapy. The medical costs for patients undergoing treatment with targeted therapy were significantly higher than for patients treated only with chemotherapy; they were especially higher in the group receiving targeted therapy early than late in the palliative setting. (4) Conclusions: The use of targeted therapy in metastatic colorectal cancer leads to significantly higher medical costs when used early in the palliative setting. No positive effects of the use of targeted therapy could be observed in this study; therefore, we suggest that targeted therapy be used in later lines of palliative therapy in metastatic colorectal cancer.
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