Haematological parameters, plasma iron concentration, and bodyweight were monitored in Melanoma-bearing Libechov Minipigs (MeLiM) from 5 to 18 weeks old. Animals with melanoma progression (P group) and spontaneous regression (SR group) were compared. The P group showed the lowest median values of red blood cell counts (RBC), haematocrit (HCT), haemoglobin concentration (HGB), and bodyweight, whereas the control white (tumour-free) pigs (C group) revealed the highest mean values of these parameters. The mean values of pigs with SR fell between the P and C groups. In addition, a stable concentration of plasma iron was found in the C group, while iron deficiency that increases with age was observed in the MeLiM groups. These results indicate that MeLiM are affected by cancer-related microcytic hypochromic anaemia. The lowest values of HGB, RBC, and HCT, together with the highest number of platelets (PLT) in the P group correspond to melanoma progression. Higher values of these parameters and lower PLT in the MeLiM pigs with SR reflected health improvement due to the destruction of melanoma cells during spontaneous regression. Monitoring of these haematological parameters can help distinguish MeLiM piglets with progression and spontaneous regression of melanoma in the early stages of postnatal development. The findings of this study correspond to findings in human patients in which cancer-related anaemia, thrombocytosis, and iron deficiency are often diagnosed.

• MeSH
• Hematologic Tests veterinary   MeSH
• Melanoma blood   physiopathology   veterinary   MeSH
• Swine, Miniature MeSH
• Skin Neoplasms blood   physiopathology   veterinary   MeSH
• Swine Diseases blood   physiopathology   MeSH
• Swine MeSH
• Disease Progression MeSH
• Neoplasm Regression, Spontaneous MeSH
• Body Weight MeSH
• Iron administration & dosage   blood   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

Maligní melanom je jedním z nejzávažnějších kožních nádorů u lidí i zvířat. Je vysoce odolný vůči konvenčním terapiím a i přes velké úsilí při vývoji nových imunoterapií došlo jen k jejich drobným vylepšením. Proto se jako ideální směr dalšího výzkumu jeví možnost vývoje imunoterapií, které by byly schopné navodit kompletní regresi nádoru, což je ideální výsledek při léčbě jakéhokoliv nádor. Bohužel podmínky potřebné k dosažení úplné regrese nejsou dosud dobře známé. V laboratoři biologie nádorů v Ústavu živočišné fyziologie a genetiky AV ČR je k dispozici model melanomu u miniaturních prasat, u kterého dochází k spontánní regresi nádorů po období progrese spojené s metastázami především do sleziny, plic a lymfatických uzlin, kdy dojde k vyléčení většiny zvířat a pouze asi 5 % umírá na progresi nádoru nebo přidružené komplikace. Další výzkum MeLiM modelu umožní získat nové poznatky o spontánní regresi melanomu a nabídne nové možnosti pro tvorbu účinnějších imunoterapií.

Malignant melanoma is one of the most serious skin cancer diseases in humans and animals. It is highly resistant to conventional therapies and despite major efforts in development of novel immunotherapies there have been only minor improvements. Therefore, an ideal further research should be led towards developing immunotherapies that would be capable of inducing a complete tumor regression. This is the ideal result of the treatment of all tumor. Unfortunately, the conditions required to achieve complete regressions are not well known yet. In the laboratory of tumor biology at the Institute of Animal Physiology and Genetics AS CR an animal model of melanoma is being researched, ie melanoma bearing Libechov minipigs, in which spontaneous tumor regression occurs after a period of progression associated with organ metastases - mainly in the spleen, lungs and lymph nodes. Most animals are completelycured, but around 10 % die of tumor progression or associated complications. Further research of MeLiM model will provide new knowledge about the spontaneous regression of melanoma and offer new possibilities for creating more effective immunotherapy.

• MeSH
• Cyprinodontiformes MeSH
• Humans MeSH
• Melanoma * MeSH
• Swine, Miniature * genetics   MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Neoplasm Regression, Spontaneous MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Regresivní změny Warthinova tumoru po aspirační biopsii tenkou jehlou jsou dobře známy. Převládajícím histopatologickým rysem je vedle dlaždicobuněčné metaplazie koagulační nekróza, která je zřídka spojena až s úplnýmsmazáním původní struktury tumoru. Absolutní raritou je nález granulomatózního zánětu, jenž kompletně absorbuje nekrotický tumor. Do dnešního dne byl zatím popsán jen jeden takový případ. Zaznamenali jsme podobný případ oboustranného Warthinova tumoru s kompletní regresí vzniklou po aspirační biopsii tenkou jehlou. Jednalo se o 61letého muže s oboustranným zduřením příušní žlázy, které se rozvíjelo asymptomaticky podobu šesti měsíců. Ultrasonografie a aspirační biopsie tenkou jehlou prokázalyWarthinův tumor. Pacient byl naplánován na chirurgický výkon, který měl být proveden o měsíc později. Osm dní před plánovanou operací u něj došlo v parotické oblasti oboustranně k rozvoji nekrotizujícího zánětu. V celkové anestezii byla provedena incize s evakuací mukopurulentního obsahu. Mikroskopický nález potvrdil nekrózu bez přítomnosti znaků charakteristických pro Warthinův tumor. Bakteriologické vyšetření i histopatologický průkaz na přítomnost plísní a bakterií v odstraněné debris bylo negativní, což vylučuje možnost, že by se mohlo jednat o bakteriálně infikovanou uzlinu či jinou afekci žlázového parenchymu.

Progressive changes of Warthin's tumour after thin needle biopsy are well known. The predominating histopathological feature is in addition to pavement metaplasia coagulation necrosis which is rarely associated withcomplete eradication of the original structure of thetumour. An absolute rarity is the finding of a granulomatous inflammation which completely absorbs the necrotic tumour. So far only one such case was described. We recorded a similar case of a bilateral Warthin tumour with complete regression which occurred after thin needle aspiration biopsy. It involved a 61-year-old man with bilateral swelling of the parotid gland which developed asymptomatically for six months. Ultrasonography and thin needle biopsy proved a Warthin tumour. The patient was indicated for surgery to be implemented in a month time. Eight days before the planned operation he developed bilaterally a necrotizing inflammation in the parotid area. Under general anaesthesia an incision was made with evacuation of mucopurulent contents. The microscopic finding confirmed necrosis without signs typical forWarthin's tumour. Bacteriological examination and histopathological evidence for the presence of molds and bacteria in the removed debris was negative which rules out the possibility that a bacterially infected node was involved or another affection of the glandular parenchyma.

• MeSH
• Biopsy MeSH
• Needles MeSH
• Middle Aged MeSH
• Humans MeSH
• Parotid Neoplasms surgery   pathology   ultrasonography   MeSH
• Necrosis diagnosis   pathology   MeSH
• Neoplasm Regression, Spontaneous MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

BACKGROUND/AIM: Spontaneous regression (SR) of tumours is a rare phenomenon not yet fully understood. The aim of this study was to investigate immune cells infiltrating progressive and SR tumours in a Lewis rat sarcoma model. MATERIALS AND METHODS: Rats were subcutaneously inoculated with rat sarcoma R5-28 (clone C4) cells. Developing tumours were obtained on day 42 and cryosections were immunohistochemically processed for detection of immune cells. RESULTS: A high density of granulocytes was found in the necrotic areas of both progressive and SR tumours. CD4+ cells and CD8+ cells were rare and sparsely dispersed in the tumour tissue without clear difference between the two types of tumours. On the contrary, CD161+ cells were abundant and evenly distributed in SR tumours, but these cells were very rare in progressive tumours. CONCLUSION: Based on the differences in number and distribution of the immune cell subpopulations, we believe that natural killer (CD161+) cells play a major role in the destruction of cancer cells during SR of tumours in this Lewis rat model.

• MeSH
• Killer Cells, Natural pathology   MeSH
• CD4-Positive T-Lymphocytes pathology   MeSH
• CD8-Positive T-Lymphocytes pathology   MeSH
• Immunohistochemistry MeSH
• Rats MeSH
• NK Cell Lectin-Like Receptor Subfamily B genetics   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Rats, Inbred Lew MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Sarcoma genetics   pathology   MeSH
• Neoplasm Regression, Spontaneous genetics   pathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Avoiding conization may reduce the risk of pre-term labor in future pregnancies, making conservative treatment of high-grade cervical dysplasia an increasingly discussed approach, especially for younger patients. However, data on the integration of individual predictive factors into routine clinical practice remain limited. PRIMARY OBJECTIVE: The primary objective of the Regression of High-Grade Squamous Intraepithelial Cervical Lesions and Associated Risk Factors (RECER) study is to assess the rate of spontaneous regression in high-grade cervical squamous dysplasia (cervical intraepithelial neoplasia [CIN] 2 and 3) and identify associated predictive factors within clinical practice, without necessitating conization. STUDY HYPOTHESIS: We hypothesize that the characterization of cervical lesions, including colposcopic findings and patient-specific factors, along with a sufficient rate of spontaneous regression, will aid in identifying a subgroup of patients who may derive the greatest benefit from conservative management of high-grade cervical lesions. TRIAL DESIGN: The RECER trial is a multi-center prospective cohort study. Patients with histologically confirmed high-grade squamous intraepithelial lesions (CIN 2 or 3) undergo colposcopic assessments every 4 months. Colposcopic images are compared to evaluate lesion dynamics. In case of progression, conization is indicated, whereas in case of regression, documentation of a biopsy with low-grade dysplasia (CIN 1) or no dysplasia is required. Patients with stable disease are further followed up. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients aged 18 to 40 years with bioptically confirmed high-grade lesion (CIN 2 or 3), a fully visible squamo-columnar junction, and a willingness to undergo conservative management can be included. Excluded are patients with unsatisfactory colposcopy, pregnancy, glandular lesions, invasive disease, or a history of treatment for severe cervical dysplasia. PRIMARY ENDPOINT: The primary end point is the regression rate of high-grade cervical dysplasia. SAMPLE SIZE: 300 patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of October 2024, a total of 127 patients have been recruited from 4 participating sites across 3 countries. Estimated date of last patient enrollment: September 2026; estimated date for results presentation: January 2028. TRIAL REGISTRATION: Clinicaltrials.gov: NCT06147388.

• MeSH
• Squamous Intraepithelial Lesions of the Cervix * diagnosis   pathology   MeSH
• Adult MeSH
• Uterine Cervical Dysplasia * diagnosis   pathology   MeSH
• Colposcopy MeSH
• Conization adverse effects   MeSH
• Humans MeSH
• Young Adult MeSH
• Multicenter Studies as Topic MeSH
• Uterine Cervical Neoplasms * diagnosis   pathology   prevention & control   MeSH
• Observational Studies as Topic MeSH
• Prospective Studies MeSH
• Risk Factors MeSH
• Remission, Spontaneous * MeSH
• Neoplasm Grading MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH

BACKGROUND: The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression. RESULTS: Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier. CONCLUSION: The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches.

• MeSH
• Bacteria genetics   MeSH
• Dysbiosis microbiology   MeSH
• Feces microbiology   MeSH
• Fusobacterium MeSH
• Melanoma * MeSH
• Microbiota * MeSH
• Tumor Microenvironment MeSH
• Swine MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Gastrointestinal Microbiome * genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cíl studie: Přehled nových znalostí, které by mohly pomoci v rozhodování o individualizované léčbě prekanceróz děložního hrdla. Typ studie: Souhrnný přehled. Název a sídlo pracoviště: Onkogynekologické centrum, Gynekologicko-porodnická klinika, Nemocnice Na Bulovce a 1. LF UK, Praha; Onkogynekologické centrum, Gynekologicko-porodnická klinika Všeobecné fakultní nemocnice a 1. LF UK, Praha. Metodika a výsledky: Prekancerózy děložního hrdla jsou zastoupeny dlaždicobuněčnými cervikálními intraepiteliálními neoplaziemi (CIN) a žlázovými adenocarcinomy in situ (AIS). Obvyklou léčbou prekanceróz děložního hrdla je konizace. Avšak některé komplikace, zvláště nežádoucí následky v pozdější graviditě, mohou doprovázet jakoukoliv chirurgickou léčbu děložního hrdla. U žen, které si přejí otěhotnět a mají CIN s nízkým rizikem transformace do invazivního karcinomu, může být terapie odložena. Výskyt blíže specifikujících faktorů by mohl pomoci rozčlenit CIN podle jejich maligního potenciálu. Význam by mohlo mít stanovení HPV genotypu, protože osud CIN 2/3 závisí na genotypu asociované HPV infekce. Cervikální léze spojené s HPV 16, 18 a 45 mají výrazně vyšší riziko progrese do invazivního karcinomu než léze asociované s jinými HR HPV genotypy. V individuálních případech by chirurgická léčba CIN 2/3 mohla být odložena u žen, které si přejí otěhotnět, pokud by léze nebyla asociována s HPV 16, 18 a 45. Použití biologických a molekulárních markerů, především p16INK4a, se pokouší upřesnit zhodnocení cervikálních lézí. Mladší věk, probíhající těhotenství, příznivý kolposkopický nález, negativní p16INK4a a neoslabená imunita jsou nezávislé faktory podporující konzervativní management. Léčba adenocarcinomu in situ se podstatně liší od managementu CIN. Závěr: Je důležité správně zhodnotit všechny upřesňující okolnosti a minimalizovat nežádoucí účinky v důsledku zbytečné či nadbytečné chirurgické léčby prekanceróz děložního hrdla.

Objective: To summarize new data which can help in decision on tailoring treatment of cervical precancerosis. Design: Review article. Setting: Department of Gynaecology and Obstetrics, First Faculty of Medicine, Charles University and Hospital Na Bulovce in Prague; Oncogynaecological Center, First Faculty of Medicine, Charles University and General University Hospital in Prague. Results: Precancerous lesions of the cervix are represented by squamous cervical intraepithelial neoplasias (CIN) and glandular adenocarcinomas in situ (AIS). The usual treatment of cervical precancerosis is conisation. However, some complications, particularly subsequent adverse pregnancy outcomes, follow all surgical treat-ments of cervix. The treatment could be postponed in women who wish to conceive and who suffer from CIN with a low risk of transformation to invasive cancer. The presence of modifying factors can help to stratify CIN lesions according to their malignant potential. The determination of detected HPV genotypes may help in this decision, because the fate of CIN 2/3 depends on the genotype of associated HPV infection. Cervical lesions associated with HPV 16, 18 or 45 are at a much higher risk of rapid progression to invasive cancers than lesions associated with other HR HPV genotypes. Surgical treatment of CIN 2/3 in women with a desire for future child-bearing can be postponed in cases non-associated with HPV 16, 18 and 45, on a case by case basis. Attempts are made to improve evaluation of the lesions by using biological and molecular markers, especially p16INK4a staining. Younger age, ongoing pregnancy, favourable colposcopic findings, negative p16INK4a staining and immunocompetency are independent factors supporting the choice of conservative management. Adenocarcinoma in situ management substantially differs from the management of CIN. Conclusion: It is important both to assess all modifying factors correctly and to minimize any harm from unnecessary surgical treatment or overtreatment of cervical precancer lesions.

• Keywords
• cervikální intraepiteliální neoplazie, HPV 45,
• MeSH
• Adenocarcinoma in Situ * diagnosis   therapy   MeSH
• Squamous Intraepithelial Lesions of the Cervix * diagnosis   genetics   therapy   MeSH
• Uterine Cervical Dysplasia * diagnosis   genetics   therapy   MeSH
• Genes, p16 MeSH
• Risk Assessment MeSH
• Precision Medicine MeSH
• Papillomavirus Infections diagnosis   genetics   MeSH
• Colposcopy MeSH
• Conization adverse effects   MeSH
• Humans MeSH
• Human papillomavirus 16 genetics   MeSH
• Human papillomavirus 18 genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Pregnancy Complications, Neoplastic MeSH
• Uterine Cervical Neoplasms diagnosis   genetics   therapy   MeSH
• Watchful Waiting MeSH
• Precancerous Conditions diagnosis   genetics   therapy   MeSH
• Neoplasm Regression, Spontaneous MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.

• MeSH
• Melanoma genetics   MeSH
• Swine, Miniature genetics   MeSH
• Disease Models, Animal MeSH
• Skin Neoplasms genetics   MeSH
• Swine genetics   MeSH
• Disease Progression MeSH
• Neoplasms, Second Primary genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• MeSH
• European Union MeSH
• Research MeSH
• Publication type
• Abstracts MeSH
• Geographicals
• Europe MeSH

• Conspectus
• Veřejné zdraví a hygiena
• NML Fields
• veřejné zdravotnictví
• politologie, politika, zdravotní politika

• About
• Commission of the European Communities. Biomedical and Health Research Programme Authority

BACKGROUND: [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a powerful tool for the imaging of various lymphomas. Despite its high FDG avidity, there is little data on PET in follicular lymphoma (FL). In this work, we present findings concerning PET at staging and posttreatment evaluation in FL. PATIENTS AND METHODS: A total of 181 PET scans were evaluated in 117 patients with FL in a retrospective study. Positron emission tomography-based results were compared with conventional staging in 82 patients. Posttreatment PET evaluation was performed in 99 patients; there were comparable progression-free survivals of PET-positive and PET-negative patients. RESULTS: Positron emission tomography showed more involvement than computed tomography (CT) with clinical examination in 41 of 82 patients (50%), less in 11 of 82 (13%); the same extension was found in 27 of 82 patients (33%), and 3 patients revealed discordant foci visible on PET only and lymphadenopathy without PET activity (P < .001). Including the results of trephine biopsy, PET finally upstaged FL in 15 of 82 patients (18%), which was projected in change of treatment strategy. There were 73 of 99 negative posttreatment PET scans; 54 of 73 PET-negative patients (74%) remain in complete remission (median follow-up, 27 months); 19 (26%) of them relapsed with median of 12 months. Fourteen of 20 (70%) PET-positive patients relapsed with a median of 4.5 months regardless of findings on CT and subsequent therapy. The difference in relapse rates between PET-positive and PET-negative patients is statistically significant (P < .001). CONCLUSION: Positron emission tomography at staging is able to substantially change treatment strategy in an important proportion of patients with FL. Persisting PET positivity after treatment predicts for a high risk of an early relapse and can identify patients with poor prognosis.

• MeSH
• Adult MeSH
• Financing, Organized MeSH
• Fluorodeoxyglucose F18 diagnostic use   MeSH
• Lymphoma, Follicular diagnosis   mortality   physiopathology   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Positron-Emission Tomography methods   MeSH
• Disease-Free Survival MeSH
• Prognosis MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Neoplasm Regression, Spontaneous MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH