Browsing by Subject "metastasis"
Now showing items 1-20 of 22
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(2020)The increased survival in malignant cutaneous melanoma (melanoma) is probably due to early diagnosis combined with improved treatment most recently. National health campaigns and screening programs for melanoma detection were started in Sweden several decades ago. We want to assess the influence of tumor characteristics, based on the TNM classification, and of second primary cancers on overall survival in melanoma. We used the Swedish Cancer Registry to assess all-cause survival in melanoma from 2003 to 2015. Hazard ratios (HRs) were estimated using multivariable Cox regression models. A total of 19,773 melanoma patients were diagnosed with TNM data. Survival showed a strong improving trend over time (p-trend
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(2021)Previous studies indicate that bilberry with high amounts of phenolic compounds can inhibit carcinogenic processes of colorectal cancer in vitro and in vivo. However, no studies have focused on the effects of bilberry on oral cancer. In this study, we aimed to examine the effects of bilberry powder on oral squamous cell carcinoma (OSCC) cells using both in vitro and in vivo assays. The effects of 0, 1, 10, and 25 mg/mL of whole bilberry powder on the viability, proliferation, migration, and invasion of OSCC (HSC-3) cells were examined and compared with 0.01 mg/mL of cetuximab. Two oral keratinocyte cell lines served as controls. Tumor area was analyzed in zebrafish microinjected with HSC-3 cells and treated with 2.5, 10, or 25 mu g/mL of bilberry powder. Metastases in the head or tail areas were counted. Bilberry powder inhibited the viability, proliferation, migration, and invasion of HSC-3 cells (p < 0.05), which was more pronounced with higher concentrations. Cetuximab had no effect on HSC-3 cell migration or invasion. Compared to controls, the tumor area in zebrafish treated with bilberry powder (10 and 25 mu g/mL) was reduced significantly (p = 0.038 and p = 0.021, respectively), but the number of fish with metastases did not differ between groups. Based on our in vitro and in vivo experiments, we conclude that whole bilberry powder has anti-tumor effects on OSCC cells.
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(2018)The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
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(2021)Tissue vasculature provides the main conduit for metastasis in solid tumours including head and neck squamous cell carcinoma (HNSCC). Vascular mimicry (VM) is an endothelial cell (EC)-independent neovascularization pattern, whereby tumour cells generate a perfusable vessel-like meshwork. Yet, despite its promising clinical utility, there are limited approaches to better identify VM in HNSCC and what factors may influence such a phenomenon in vitro. Therefore, we employed different staining procedures to assess their utility in identifying VM in tumour sections, wherein mosaic vessels may also be adopted to further assess the VM-competent cell phenotype. Using 13 primary and metastatic HNSCC cell lines in addition to murine- and human-derived matrices, we elucidated the impact of the extracellular matrix, tumour cell type, and density on the formation and morphology of cell-derived tubulogenesis in HNSCC. We then delineated the optimal cell numbers needed to obtain a VM meshwork in vitro, which revealed cell-specific variations and yet consistent expression of the EC marker CD31. Finally, we proposed the zebrafish larvae as a simple and cost-effective model to evaluate VM development in vivo. Taken together, our findings offer a valuable resource for designing future studies that may facilitate the therapeutic exploitation of VM in HNSCC and other tumours.
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(2021)No data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS >= 12,
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(2019)Background: Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastasesmay reduce recurrences and improve survival. The choice of best candidates for adjuvant chemotherapy in this setting is controversial, especially when a single lung metastases (SLM) is resected. The aim of this study is to evaluate the risk of recurrence after radical resection for single lung metastasis from CRC. Patients and methods: Demographic, clinical, and pathological data were retrospectively collected for patients radically operated on for single pulmonary metastasis from CRC in 4 centers. Survival was computed by Kaplan-Meyer methods. Chi-square, log-rank test, and formultivariate analysis, Cox-regression and binary logistic regression were used when indicated. Results: The sample consisted of 344 patients, mean age 65 yrs. Overall 5 yrs survival was 61.9%. Recurrence occurred in 113 pts (32.8%). At univariate analysis, age > 70 (p = 0.046) and tumor size > 2 cm (p = 0.038) were predictive of the worst survival chance, while synchronous lung metastasis (p = 0.039), previous resection of extrathoracic metastasis (p = 0.017), uptake at FDG-PET scan (p = 0.006) and short (<12 months) disease-free interval (DFI) prior to lung metastasectomy (p = 0.048) were risk factors for recurrence. At multivariate analysis, only high CEA (> 4 ng/mL) was associated with worst survival (HR: 4.3, p = 0.014), while prior abdominal surgery (HR: 3, p = 0.033), PET positivity (HR: 2.7, p = 0.041), and DFI > 12 months (HR: 0.14, p <0.001) confirmed to predict recurrence of disease. Conclusions: Surgical resection of solitary lung metastases from CRC is associated with prolonged survival. High value of CEA, PET positivity, previous extrathoracic resected metastasis, and short (
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(2018)Triple‐negative breast cancer (TNBC) is a kind of aggressive malignancy with fast metastatic behavior. Herein, a nanosystem loaded with a near‐infrared (NIR) agent is developed to achieve chemo‐photothermal combination therapy for inhibiting tumor growth and metastasis in TNBC. The NIR agent of ultrasmall sized copper sulfide nanodots with strong NIR light‐absorbing capability is entrapped into the doxorubicin‐contained temperature‐sensitive polymer‐based nanosystem by a self‐assembled method. The temperature sensitive nanoclusters (TSNCs) can significantly enhance the drug penetration depth and significantly kill the cancer cells under the near‐infrared laser irradiation. Importantly, it is plausible that the tumor penetrating nanosystem combined with NIR laser irradiation can prevent lung and liver metastasis via extermination of the cancer stem cells. The in vivo characteristics, evaluated by photoacoustic imaging, pharmacokinetics, and biodistribution, confirm their feasibility for tumor treatment owing to their long blood circulation time and high tumor uptake. Thanks to the high tumor uptake and highly potent antitumor efficacy, the doxorubicin‐induced cardiotoxicity can be avoided when the TSNC is used. Taken together, it is believed that the nanosystem has excellent potential for clinical translation.
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(2019)Sarcomas are deadly malignant tumors of mesenchymal origin occurring at all ages. The expression and function of the membrane-type matrix metalloproteinase MMP14 is closely related to the mesenchymal cell phenotype, and it is highly expressed in most sarcomas. MMP14 regulates the activity of multiple extracellular and plasma membrane proteins, influencing cell-cell and cell-extracellular matrix (ECM) communication. This regulation mediates processes such as ECM degradation and remodeling, cell invasion, and cancer metastasis. Thus, a comprehensive understanding of the biology of MMP14 in sarcomas will shed light on the mechanisms controlling the key processes in these diseases. Here, we provide an overview of the function and regulation of MMP14 and we discuss their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas.
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(2022)Simple Summary Head and neck squamous cell carcinoma (HNSCC) is a group of common and aggressive tumors. Recently, oral microbiota has been credited as an important player in carcinogenesis. However, the available knowledge is not always consistent and sometimes conflicting. Therefore, the present comprehensive systematic review of the current clinical reports was conducted to evaluate the role of oral microbiota in HNSCC. Importantly, this study addresses whether oral microbiota targeting could provide diagnostic, prognostic or therapeutic utility in cancer patients. We also discussed the current limitations of this newly emerging field and the potential related strategies for the management of patients with HNSCC and possibly other solid tumors. Head and neck squamous cell carcinoma (HNSCC) comprises the majority of tumors in head and neck tissues. The prognosis of HNSCC has not significantly improved for decades, signifying the need for new diagnostic and therapeutic targets. Recent evidence suggests that oral microbiota is associated with carcinogenesis. Thus, we conducted a comprehensive systematic review to evaluate the current evidence regarding the role of oral microbiota in HNSCC and whether their targeting may confer diagnostic, prognostic or therapeutic utility. Following the screening of 233 publications retrieved from multiple databases, 34 eligible studies comprising 2469 patients were compiled and critically appraised. Importantly, many oral pathogens, such as Porphyromonas gingivalis and Fusobacterium nucleatum were linked to certain oral potentially malignant lesions and various types of HNSCC. Furthermore, we summarized the association between the expression profiles of different oral bacterial species and their tumorigenic and prognostic effects in cancer patients. We also discussed the current limitations of this newly emerging area and the potential microbiota-related strategies for preventing and treating HNSCC. Whilst many clinical studies are underway to unravel the role of oral microbiota in cancer, the limited available data and experimental approaches reflect the newness of this promising yet challenging field.
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(Helsingin yliopisto, 2020)Melanooma on ihosyöpä, jonka ennuste on ihon syövistä huonoin. Melanooman paksuus on merkittävin ennustetekijä metastasoinnin suhteen. Pinnallisiin melanoomiin lasketaan kuuluvaksi paksuudeltaan enintään 1 mm paksut melanoomat. Pinnalliset melanoomat metastasoivat harvoin, mutta metastasoidessa potilaan ennuste huonontuu selkeästi. Melanooma metastasoi tavallisimmin imuteitä pitkin ensiksi paikallisiin imusolmukkeisiin. Mahdollista metastasointia pyritään selvittämäänvartijaimusolmuketutkimuksella. Tämän tutkielman tavoitteena oli selvittää vuosina 2010-2013 Helsingin ja Uudenmaan sairaanhoitopiirissä (HUS) todettujen pinnallisten melanoomapotilaiden selviytymistä ja vartijaimusolmuketutkimuksen tuloksia. 599 potilaalla todettiin pinnallinen melanooma. Näistä potilaista 192:lle (32,1%) tehtiin vartijaimusolmuketutkimus. Positiivisia löydöksiä oli 10 (5,2%). Positiivisen tuloksen saaneista neljällä (40,0%) tauti metastasoi seuranta-aikana, negatiivisen tuloksen saaneista kolmella (1,6%). Komplikaatioita vartijaimusolmuketutkimuksesta todettiin sairauskertomusmerkintöjen perusteella 39 potilaalla (20,3%). Systeemimetastasointi todettiin 11 potilaalla (1,8%). Imusolmukemetastasoinnin riskitekijöiksi nousivat Breslow-luokka > 0,8 mm sekä korkea Clark-luokitus (IV-V). Ohuissa pinnallisissa, <0.8mm paksuissa melanoomissa ulseraatio ja regressio vaikuttaisivat nostavan metastasointiriskiä. Pinnallinen melanooma metastasoi harvoin vartijaimusolmukkeeseen, mutta systeemimetastaasin todennäköisyys vaikuttaa kasvavan positiivisen vartijalöydöksen myötä huomattavasti. Aineiston pienen koon vuoksi tarkkoja päätelmiä vartijaimusolmuketutkimuksen kriteereistä ei ole mahdollista tehdä. Rajatapauksissa potilastapaukset on syytä käydä läpi moniammatillisen ryhmän toimesta. (166 sanaa)
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Recurrent and Metastatic Cutaneous Squamous Cell Carcinomas in a Cohort of 774 Patients in Finland (2020)Dermato-Venereologica Recognising patients with high risk cutaneous squamous cell carcinomas is essential in planning effective monitoring. The aim of this study was to determine the rate of local recurrences and metastases of cutaneous squamous cell carcinomas in a previously defined patient cohort in Finland. Pathology database search was performed to identify cutaneous squamous cell carcinoma patients and their medical records were reviewed. The cohort consisted of 774 patients with 1,131 cutaneous squamous cell carcinoma tumours. Overall, 4.2% (48/1,131) of the tumours were metastatic and 2.2% (25/1,131) had a local recurrence. Three of the metastatic tumours and 8 of the recurrent tumours had an invasion depth of
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(2018)Background: ODM-201, a new androgen receptor antagonist for treatment of metastatic castration-resistant prostate cancer (mCRPC), demonstrated antitumour activity and acceptable tolerability in phase 1/2 trials. Objective: To determine the antitumour activity and safety profile of extended treatment with ODM-201 in men with mCRPC. Design, setting, and participants: ARADES and ARAFOR trials with ODM-201 enrolled chemotherapy-naïve and CYP17 inhibitor (CYP17i)-naïve mCRPC patients. Both trials had extended follow-up. Here we report results for chemotherapy-naïve and CYP17i-naïve patients from both trials (data cutoff October 2014 for ARADES and April 2015 for ARAFOR) after extended follow-up. Intervention: A total of 41 chemotherapy-naïve and CYP17i-naïve patients received oral ODM-201 twice daily (total daily dose of 1200, 1400 or 1800 mg). Outcome measurements and statistical analysis: Antitumour activity was assessed in terms of prostate-specific antigen (PSA) declines and PSA/radiographic progression. Safety was assessed until disease progression and/or drug discontinuation due to any intolerable adverse event (AE). Results and limitations: ODM-201 safety data after a median treatment time of 13.5 mo (95% confidence interval [CI] 9.7–15.6, interquartile range [IQR] 7.5–22.0) were similar to those reported in the main ARADES and ARAFOR trials. The overall AE incidence was 80.5% (n = 33/41), with 58.5% (n = 24/41) of patients experiencing only grade 1–2 AEs. The most common AEs were fatigue, back pain, diarrhoea, nausea, and pain in extremity. The median times to PSA and radiological progression were 12.4 mo (95% CI 6.3–18.2, IQR 5.5–22.0) and 15.3 mo (95% CI 9.5–not reached [NR], IQR 6.3–NR), respectively. Conclusions: Extended treatment with ODM-201 (1200–1800 mg/d) was well tolerated, with no new safety concerns, and provided evidence of sustained antitumour activity in chemotherapy-naïve and CYP17i-naïve patients with mCRPC. Patient summary: Prolonged treatment with high doses of ODM-201 was well tolerated and provided long-lasting disease control in patients with mCRPC. ODM-201 represents a therapeutic treatment option for mCRPC. The ARAFOR trial (including the follow-up stage) and the follow-up component of the ARADES trial are registered with ClinicalTrials.gov as trial numbers NCT01784757 and NCT01429064. Extended treatment with ODM-201 was well tolerated and provided long-lasting disease control in chemotherapy- naïve and CYP17 inhibitor-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). ODM-201 may represent an additional effective treatment option for mCRPC. © 2017 European Association of Urology
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(2020)Background: Survival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease. Methods: Data for melanoma and any SPCs were obtained from the Swedish Cancer Registry for years 2003 through 2015, including clinical TNM classification. SPCs were grouped into three 'prognostic groups' based on 5-year relative survival of these cancers as first primary cancer. Kaplan-Meier survival curves were generated and hazard ratios were estimated using Cox regression, adjusted for a number of variables and treating diagnosis of SPC as a time-dependent variable. Results: The total number of first melanoma patients was 28,716 followed by 3,202 (11.1%) SPCs, 1/3 of which had a second melanoma while 2/3 had other SPCs. Among men diagnosed at age over 70 years, who survived at least 10 years, 31.4% had SPC. HRs (95% CI) for survival increased systematically from the reference rate of 1.00 (no SPC) to 1.59 (1.35-1.87) with SPC of good prognosis (78.6% of SPCs) to 3.49 (2.58-4.72) of moderate prognosis (12.0%) and to 7.93 (5.50-11.44) of poor prognosis (9.4%). In patients without SPC, the HRs increased to 2.62 (2.02-3.39) with any nodal metastases and to 5.88 (4.57-7.57) with any distant metastases compared to patients without local or distant metastases. Conclusion: The data showed that SPCs are an increasingly common negative prognostic factor for melanoma. Future attempts to improve melanoma survival need to target SPCs.
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(2020)The aim of this retrospective study was to analyse a consecutive series of patients with oral and oropharyngeal carcinoma who had had sentinel lymph node biopsy (SLNB) at our hospital during 2008-2017. A total of 70 patients with clinically and radiologically confirmed primary oral (n = 67) or oropharyngeal (n = 3) carcinoma, with no signs of metastatic lymph nodes preoperatively (clinically N0) were included. Patients' clinical and personal data, characteristics of the tumours, sentinel lymph node (SLN) status and outcomes were recorded. Eight patients had invaded SLN. Two patients with clear sentinel lymph node biopsies had recurrences in the cervical lymph nodes with no new primary tumour as origin. The negative predictive value (NPV) and sensitivity for SLNB were 97% and 80%, respectively. The depth of invasion was an individual predictor for cervical lymph node metastasis (p = 0.043). Single photo emission computed tomography (SPECT) detected fewer SLN in patients with invaded lymph nodes than in patients with clear lymph nodes (p = 0.018). Our data support the use of SLNB as a minimally invasive method for staging the cervical lymph nodes among patients with cN0 oral and oropharyngeal carcinoma. Our results further confirm that greater depth of invasion is associated with cervical lymph node metastases. (c) 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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(2020)The aim of this retrospective study was to analyse a consecutive series of patients with oral and oropharyngeal carcinoma who had had sentinel lymph node biopsy (SLNB) at our hospital during 2008-2017. A total of 70 patients with clinically and radiologically confirmed primary oral (n = 67) or oropharyngeal (n = 3) carcinoma, with no signs of metastatic lymph nodes preoperatively (clinically N0) were included. Patients' clinical and personal data, characteristics of the tumours, sentinel lymph node (SLN) status and outcomes were recorded. Eight patients had invaded SLN. Two patients with clear sentinel lymph node biopsies had recurrences in the cervical lymph nodes with no new primary tumour as origin. The negative predictive value (NPV) and sensitivity for SLNB were 97% and 80%, respectively. The depth of invasion was an individual predictor for cervical lymph node metastasis (p = 0.043). Single photo emission computed tomography (SPECT) detected fewer SLN in patients with invaded lymph nodes than in patients with clear lymph nodes (p = 0.018). Our data support the use of SLNB as a minimally invasive method for staging the cervical lymph nodes among patients with cN0 oral and oropharyngeal carcinoma. Our results further confirm that greater depth of invasion is associated with cervical lymph node metastases. (c) 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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(2021)The transcription factor SOX9 is a key regulator of multiple developmental processes and is frequently re-expressed in non-small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histotypes has, however, remained elusive. We show that SOX9 expression relates to poor overall survival and invasive histopathology in human non-mucinous adenocarcinoma and is absent in murine early minimally invasive and low in human in situ adenocarcinoma. Interestingly, despite wide SOX9 expression across advanced NSCLC histotypes, its genetic deletion in the murine Kras(G12D);Lkb1(fl/fl) model selectively disrupted only the growth of papillary NSCLC, without affecting the initiation of precursor lesions or growth of mucinous or squamous tissue. Spatial tissue phenotyping indicated a requirement of SOX9 expression for the progression of surfactant protein C-expressing progenitor cells, which gave rise to papillary tumours. Intriguingly, while SOX9 expression was dispensable for squamous tissue formation, its loss in fact led to enhanced squamous tumour metastasis, which was associated with altered collagen IV deposition in the basement membrane. Our work therefore demonstrates histopathology-selective roles for SOX9 in NSCLC progression, namely as a promoter for papillary adenocarcinoma progression, but an opposing metastasis-suppressing role in squamous histotype tissue. This attests to a pleiotropic SOX9 function, linked to the cell of origin and microenvironmental tissue contexts. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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(2019)Objective To evaluate the impact of postoperative radiotherapy (PORT) and chemotherapy on survival in salivary gland cancer (SGC) treated with curative-intent local resection and neck dissection. Study Design Retrospective population-based cohort study. Setting National Cancer Database. Subjects and Methods Patients with SGC who were undergoing surgery were identified from the National Cancer Database between 2004 and 2013. Neck dissection removing a minimum of 10 lymph nodes was required. Because PORT violated the proportional hazards assumption, this variable was treated as a time-dependent covariate. Results Overall, 4145 cases met inclusion criteria (median follow-up, 54 months). PORT was associated with improved overall survival in multivariable analysis, both 9 months (HR, 0.75; 95% CI, 0.66-0.86; P <.001). In propensity score-matched cohorts, 5-year overall survival was 67.1% and 60.6% with PORT and observation, respectively (P <.001). Similar results were observed in landmark analysis of patients surviving at least 6 months following diagnosis. Adjuvant chemotherapy was not associated with improved survival (HR, 1.15; 95% CI, 0.99-1.34; P = .06). Conclusion PORT, but not chemotherapy, is associated with improved survival among patients with SGC for whom neck dissection was deemed necessary. These results are not applicable to low-risk SGCs not requiring neck dissection.
