Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.Thi...Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.展开更多
BACKGROUNDAs the population of colorectal cancer(CRC)survivors continues to grow,thedemand for effective,evidence-based post-treatment strategies becomes increasinglyurgent.Despite robust evidence linking lifestyle fa...BACKGROUNDAs the population of colorectal cancer(CRC)survivors continues to grow,thedemand for effective,evidence-based post-treatment strategies becomes increasinglyurgent.Despite robust evidence linking lifestyle factors to canceroutcomes,there remains no established consensus on the optimal nutritional andphysical activity(PA)guidelines for disease-free CRC survivors.AIMTo demonstrate that structured lifestyle interventions,specifically tailored dietaryand PA programs,can significantly improve behavioral targets as well as diseasefreeand overall survival(OS).METHODSWe designed a 2×2 factorial phase II randomized controlled trial to compare the effects of dietary and PA interventions with standard care.RESULTSA total of 300 CRC survivors in complete remission will be recruited from oncology centers in Misurata and Zliten(Libya)and the Habib Bourguiba University Hospital(Tunisia).Participants will be randomized into four groups:Combined intervention,diet-only,PA-only,or usual care.They will be followed for 24 months,with outcomesincluding disease-free survival,OS,and quality of life.Ethical approval has been obtained(Sfax ID:61/24;Misurata ID:04/2023),and the trial is registered at ClinicalTrials.gov(NCT06194786).CONCLUSIONThis study will provide crucial region-specific evidence on the feasibility and effectiveness of lifestyle interventionsin CRC survivorship care.By evaluating the role of a high-fiber,low-red meat diet and structured PA,we aim todemonstrate the potential of these behaviors to improve survival outcomes and support their integration intofuture clinical practice guidelines.展开更多
We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg...We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg pain. Computed tomography (CT) showed an intracanalar mass with calcification or ossification, which most likely originated from the vertebral body at the L1/2 level epidural space. On a T1-weighted gadolinium magnetic resonance image, the capsule of the mass was enhanced and not only the content of the mass but also that of the L2 vertebral body were partially and slightly enhanced. The final pathological diagnosis was disc herniation with end-plate fracture and secondary ossification. A combination of these pathological conditions as accompanied by both end-plate fractures and extensive secondary ossifications has not been previously reported. This rare pathological condition needs to be recognized as a differential diagnosis.展开更多
Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium p...Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium pyrophosphate)guides osteogenesis beyond the physiological envelope.In a sheep model,hollow dome-shaped constructs were placed directly over the occipital bone.At 12 months,large amounts of bone(~75%)occupy the hollow space with strong evidence of ongoing remodelling.Features of both compact bone(osteonal/osteon-like arrangements)and spongy bone(trabeculae separated by marrow cavities)reveal insights into function/need-driven microstructural adaptation.Pores within the CaP also contain both woven bone and vascularised lamellar bone.Osteoclasts actively contribute to CaP degradation/removal.Of the constituent phases,only calcium pyrophosphate persists within osseous(cutting cones)and non-osseous(macrophages)sites.From a translational perspective,this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.展开更多
基金supported by the Russian Science Foundation,project no.23-14-00285。
文摘Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.
文摘BACKGROUNDAs the population of colorectal cancer(CRC)survivors continues to grow,thedemand for effective,evidence-based post-treatment strategies becomes increasinglyurgent.Despite robust evidence linking lifestyle factors to canceroutcomes,there remains no established consensus on the optimal nutritional andphysical activity(PA)guidelines for disease-free CRC survivors.AIMTo demonstrate that structured lifestyle interventions,specifically tailored dietaryand PA programs,can significantly improve behavioral targets as well as diseasefreeand overall survival(OS).METHODSWe designed a 2×2 factorial phase II randomized controlled trial to compare the effects of dietary and PA interventions with standard care.RESULTSA total of 300 CRC survivors in complete remission will be recruited from oncology centers in Misurata and Zliten(Libya)and the Habib Bourguiba University Hospital(Tunisia).Participants will be randomized into four groups:Combined intervention,diet-only,PA-only,or usual care.They will be followed for 24 months,with outcomesincluding disease-free survival,OS,and quality of life.Ethical approval has been obtained(Sfax ID:61/24;Misurata ID:04/2023),and the trial is registered at ClinicalTrials.gov(NCT06194786).CONCLUSIONThis study will provide crucial region-specific evidence on the feasibility and effectiveness of lifestyle interventionsin CRC survivorship care.By evaluating the role of a high-fiber,low-red meat diet and structured PA,we aim todemonstrate the potential of these behaviors to improve survival outcomes and support their integration intofuture clinical practice guidelines.
文摘We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg pain. Computed tomography (CT) showed an intracanalar mass with calcification or ossification, which most likely originated from the vertebral body at the L1/2 level epidural space. On a T1-weighted gadolinium magnetic resonance image, the capsule of the mass was enhanced and not only the content of the mass but also that of the L2 vertebral body were partially and slightly enhanced. The final pathological diagnosis was disc herniation with end-plate fracture and secondary ossification. A combination of these pathological conditions as accompanied by both end-plate fractures and extensive secondary ossifications has not been previously reported. This rare pathological condition needs to be recognized as a differential diagnosis.
文摘Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium pyrophosphate)guides osteogenesis beyond the physiological envelope.In a sheep model,hollow dome-shaped constructs were placed directly over the occipital bone.At 12 months,large amounts of bone(~75%)occupy the hollow space with strong evidence of ongoing remodelling.Features of both compact bone(osteonal/osteon-like arrangements)and spongy bone(trabeculae separated by marrow cavities)reveal insights into function/need-driven microstructural adaptation.Pores within the CaP also contain both woven bone and vascularised lamellar bone.Osteoclasts actively contribute to CaP degradation/removal.Of the constituent phases,only calcium pyrophosphate persists within osseous(cutting cones)and non-osseous(macrophages)sites.From a translational perspective,this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.
