The present study aimed to investigate the association between matrix metalloproteinase-1 (MMP-1) and early gastric cancer (EGC), while also evaluating the effect of MMP-1 on gastric cancer cell proliferation and migration. Transcriptome RNA sequencing and database analysis were conducted to assess the relationship between MMP-1 expression and EGC. Differences in MMP-1 expression between clinical EGC samples and paracancerous tissues were detected using fluorescence quantitative polymerase chain reaction (PCR). In N87 gastric cancer cells, changes in proliferation- and migration-related indicator expression were determined. Gene sequencing revealed differential expression of MMP-1 in early and advanced gastric cancers. Furthermore, enhanced MMP-1 expression was observed in early and advanced gastric cancer tissues, exhibiting a positive correlation with the malignant phenotype in gastric cancer cell lines. Fluorescence quantitative PCR revealed considerably higher MMP-1 expression in EGC tissues than in paracancerous tissues. CCK8 and EdU assays demonstrated a significant increase in N87 cell proliferation on MMP-1 upregulation and a decrease on its downregulation. The scratch assay results demonstrated a corresponding enhancement in N87 cell migratory capacity with MMP-1 upregulation, which was attenuated on its downregulation. Western blot experiments revealed a decrease in the expression of the epithelial-mesenchymal transition-related protein E-cadherin after MMP-1 upregulation, while vimentin expression significantly increased. Conversely, the downregulation of MMP-1 led to opposite outcomes. Overall, MMP-1 emerges as a potential biomarker for EGC diagnosis and plays a crucial role in the regulation of N87 gastric cancer cell proliferation and migration.
{"title":"Matrix metalloproteinase-1 as a potential biomarker for early gastric cancer detection and its effect on gastric cancer cell proliferation and migration","authors":"Ke Yi, Yan Hu, Xiaoli Zhu, Qing Li","doi":"10.36922/td.1973","DOIUrl":"https://doi.org/10.36922/td.1973","url":null,"abstract":"The present study aimed to investigate the association between matrix metalloproteinase-1 (MMP-1) and early gastric cancer (EGC), while also evaluating the effect of MMP-1 on gastric cancer cell proliferation and migration. Transcriptome RNA sequencing and database analysis were conducted to assess the relationship between MMP-1 expression and EGC. Differences in MMP-1 expression between clinical EGC samples and paracancerous tissues were detected using fluorescence quantitative polymerase chain reaction (PCR). In N87 gastric cancer cells, changes in proliferation- and migration-related indicator expression were determined. Gene sequencing revealed differential expression of MMP-1 in early and advanced gastric cancers. Furthermore, enhanced MMP-1 expression was observed in early and advanced gastric cancer tissues, exhibiting a positive correlation with the malignant phenotype in gastric cancer cell lines. Fluorescence quantitative PCR revealed considerably higher MMP-1 expression in EGC tissues than in paracancerous tissues. CCK8 and EdU assays demonstrated a significant increase in N87 cell proliferation on MMP-1 upregulation and a decrease on its downregulation. The scratch assay results demonstrated a corresponding enhancement in N87 cell migratory capacity with MMP-1 upregulation, which was attenuated on its downregulation. Western blot experiments revealed a decrease in the expression of the epithelial-mesenchymal transition-related protein E-cadherin after MMP-1 upregulation, while vimentin expression significantly increased. Conversely, the downregulation of MMP-1 led to opposite outcomes. Overall, MMP-1 emerges as a potential biomarker for EGC diagnosis and plays a crucial role in the regulation of N87 gastric cancer cell proliferation and migration.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"123 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140378817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shah Kamal, Amanullah Amanullah, Qingqing Wang, Najeeb Ullah, Gohar Mushtaq, Muhammad Nasir Iqbal, Mohammad Amjad Kamal
Human CXCR1 is a G-protein α subunit i (Gαi)-coupled receptor (GPCR) that plays an important role in promoting leukocyte recruitment and activation in inflammatory regions; thus, its genetic contribution to human disorders warrants further investigation. In this study, we investigated whether oncogenic missense mutations in CXCR1 would affect its activity and hinder its ability to interact with its ligand. This study utilized a bioinformatics approach and employed precise and thorough computational methods to gain insights into the molecular characteristics of mutated CXCR1 that are responsible for causing diseases. I-TASSER was used to construct a mutant model with the required mutations. Schrödinger’s Desmond software was used to evaluate how mutations affect the stability and function of proteins. In this study, 299 CXCR1 missense mutations were examined; 53 of these were reported to be disease-causing, five of which were directly associated with cancer. The impact of the three cancer-causing mutations (N57D, R135C, and P302S) on protein stability and function was subsequently examined through computational analysis. Positions N57, R135, and P302 were determined to be highly conserved, and substitutions with aspartic acid (D), cysteine (C), and serine (S), respectively, could impair CXCR1 activity. Hence, our findings suggested that these mutations could alter CXCR1 ligand binding activity, lowering the risk of cancer and helping patients defend against pathogen invasion during a neutrophil-mediated innate immune response.
{"title":"Bioinformatics analysis of missense mutations in CXCR1 implicates altered protein stability and function","authors":"Shah Kamal, Amanullah Amanullah, Qingqing Wang, Najeeb Ullah, Gohar Mushtaq, Muhammad Nasir Iqbal, Mohammad Amjad Kamal","doi":"10.36922/td.2512","DOIUrl":"https://doi.org/10.36922/td.2512","url":null,"abstract":"Human CXCR1 is a G-protein α subunit i (Gαi)-coupled receptor (GPCR) that plays an important role in promoting leukocyte recruitment and activation in inflammatory regions; thus, its genetic contribution to human disorders warrants further investigation. In this study, we investigated whether oncogenic missense mutations in CXCR1 would affect its activity and hinder its ability to interact with its ligand. This study utilized a bioinformatics approach and employed precise and thorough computational methods to gain insights into the molecular characteristics of mutated CXCR1 that are responsible for causing diseases. I-TASSER was used to construct a mutant model with the required mutations. Schrödinger’s Desmond software was used to evaluate how mutations affect the stability and function of proteins. In this study, 299 CXCR1 missense mutations were examined; 53 of these were reported to be disease-causing, five of which were directly associated with cancer. The impact of the three cancer-causing mutations (N57D, R135C, and P302S) on protein stability and function was subsequently examined through computational analysis. Positions N57, R135, and P302 were determined to be highly conserved, and substitutions with aspartic acid (D), cysteine (C), and serine (S), respectively, could impair CXCR1 activity. Hence, our findings suggested that these mutations could alter CXCR1 ligand binding activity, lowering the risk of cancer and helping patients defend against pathogen invasion during a neutrophil-mediated innate immune response.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140387938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Momoko Yoshikawa, T. Karube, Hiroki Nagamine, W. Muraoka, Hideki Kizu, H. Kawana, T. Nakagawa, S. Asoda
Odontogenic myxofibroma of the jawbone is a rarity in children, and there are few reports of cases with long-term follow-up, which mainly describe the growth process of odontogenic myxofibroma. We herein report a case of odontogenic myxofibroma that arose in the mandibular angle of a pediatric patient with a long-term follow-up of more than 14 years. The patient, when he was 10-years-old, first approached us with a complaint of painless swelling in the right mandibular angle that was palpable and showed bone-like hardness. Computed tomography revealed an ill-defined bone defect measuring 20 mm in diameter with bone protrusion in the margin. A biopsy was performed to differentiate the mass from osteosarcoma, giving a preliminary diagnosis of odontogenic myxofibroma or chondromyxofibroma. Therefore, tumorectomy was performed under general anesthesia. We curetted the bone surrounding the tumor and filled defect with iliac cancellous bone. The final diagnosis was odontogenic myxofibroma. At present, 14 years after the surgery, the patient had experienced an uneventful post-operative course without recurrence.
{"title":"Odontogenic myxofibroma arising in the mandibular angle of a child with long-term follow-up: A case report","authors":"Momoko Yoshikawa, T. Karube, Hiroki Nagamine, W. Muraoka, Hideki Kizu, H. Kawana, T. Nakagawa, S. Asoda","doi":"10.36922/td.2096","DOIUrl":"https://doi.org/10.36922/td.2096","url":null,"abstract":"Odontogenic myxofibroma of the jawbone is a rarity in children, and there are few reports of cases with long-term follow-up, which mainly describe the growth process of odontogenic myxofibroma. We herein report a case of odontogenic myxofibroma that arose in the mandibular angle of a pediatric patient with a long-term follow-up of more than 14 years. The patient, when he was 10-years-old, first approached us with a complaint of painless swelling in the right mandibular angle that was palpable and showed bone-like hardness. Computed tomography revealed an ill-defined bone defect measuring 20 mm in diameter with bone protrusion in the margin. A biopsy was performed to differentiate the mass from osteosarcoma, giving a preliminary diagnosis of odontogenic myxofibroma or chondromyxofibroma. Therefore, tumorectomy was performed under general anesthesia. We curetted the bone surrounding the tumor and filled defect with iliac cancellous bone. The final diagnosis was odontogenic myxofibroma. At present, 14 years after the surgery, the patient had experienced an uneventful post-operative course without recurrence.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"59 40","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140230672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme Prado Costa, Petra Karla Böckelmann, Renato Prado Costa, C. H. Schaal, Fernando César Sala, André Pereira Vanni, Leandro Luiz Lopes de Freitas, J. C. C. Alonso, G. Camargo, Gabriela de Oliveira, B. R. de Souza, A. Billis, Wagner José Fávaro
Bladder cancer (BC) stands as the second most common urinary tract malignancy. Recent years have witnessed a growing interest in investigating energy metabolism to help with better understanding the energy sources harnessed by tumor cells. The aims of the present study are to feature and compare cell energy metabolism profiles among different histological grades of non-muscle-invasive BC (NMIBC) by adjusting their bioenergetic cellular indexes based on the specific tumor types. Forty urinary bladder tissue samples from patients both with and without a diagnosis of urothelial lesions were collected. Subsequently, samples were categorized into four groups comprising ten samples each, namely: normal (no urothelial lesions) group, low-grade pTa group, high-grade pTa group, and high-grade pT1 group. These tissue samples were examined by means of immunohistochemistry and Western blotting to assess proteins involved in cell energy metabolism. Based on the current findings, the normal and low-grade pTa groups presented clear preference for the oxidative phosphorylation pathway; consequently, they recorded high bioenergetic cellular index. On the other hand, both the high-grade pTa and pT1 groups presented proclivity towards the glycolytic pathway. These observations, mainly those associated with the bioenergetic cellular index, hold promising clinical relevance in the management of BC. Given the often aggressive and potentially debilitating nature of treatments applied to this neoplasia type, the current study offers invaluable insights on this topic and emphasizes changes in the bioenergetic cellular index at different NMIBC grades, which could serve as potential markers for both the diagnosis and prognosis of NMIBC patients.
{"title":"Profiling energy metabolism in normal bladder tissue and non-muscle-invasive bladder cancer cases of different histological grades","authors":"Guilherme Prado Costa, Petra Karla Böckelmann, Renato Prado Costa, C. H. Schaal, Fernando César Sala, André Pereira Vanni, Leandro Luiz Lopes de Freitas, J. C. C. Alonso, G. Camargo, Gabriela de Oliveira, B. R. de Souza, A. Billis, Wagner José Fávaro","doi":"10.36922/td.2290","DOIUrl":"https://doi.org/10.36922/td.2290","url":null,"abstract":"Bladder cancer (BC) stands as the second most common urinary tract malignancy. Recent years have witnessed a growing interest in investigating energy metabolism to help with better understanding the energy sources harnessed by tumor cells. The aims of the present study are to feature and compare cell energy metabolism profiles among different histological grades of non-muscle-invasive BC (NMIBC) by adjusting their bioenergetic cellular indexes based on the specific tumor types. Forty urinary bladder tissue samples from patients both with and without a diagnosis of urothelial lesions were collected. Subsequently, samples were categorized into four groups comprising ten samples each, namely: normal (no urothelial lesions) group, low-grade pTa group, high-grade pTa group, and high-grade pT1 group. These tissue samples were examined by means of immunohistochemistry and Western blotting to assess proteins involved in cell energy metabolism. Based on the current findings, the normal and low-grade pTa groups presented clear preference for the oxidative phosphorylation pathway; consequently, they recorded high bioenergetic cellular index. On the other hand, both the high-grade pTa and pT1 groups presented proclivity towards the glycolytic pathway. These observations, mainly those associated with the bioenergetic cellular index, hold promising clinical relevance in the management of BC. Given the often aggressive and potentially debilitating nature of treatments applied to this neoplasia type, the current study offers invaluable insights on this topic and emphasizes changes in the bioenergetic cellular index at different NMIBC grades, which could serve as potential markers for both the diagnosis and prognosis of NMIBC patients.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"44 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140228963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teng Liu, Jinxin Ye, Chunnan Hu, Zongbo Zhang, Zhuomiao Ye, Jiangnan Liao, Mingzhu Yin
Spatially resolved transcriptomics was honored as the Method of the Year 2020 by Nature Methods. This approach allows biologists to precisely discern mRNA expression at the cellular level within structurally preserved tissues. Leveraging artificial intelligence in spatial transcriptomic analysis enhances the understanding of cellular-level biological interactions and offers novel insights into intricate tissues, such as tumor microenvironments. Nevertheless, numerous existing clustering algorithms employing deep learning exhibit the potential for enhancement. In this paper, we focus on graph deep learning-based spatial domain identification for spatial transcriptomics (ST) data from multiple tumors. This identification enables the recognition of cell subpopulations in distinct spatial coordinates, aiding further studies on tumor progression, such as cell-cell communication, pseudo-time trajectory inference, and single-cell deconvolution. Initially, the gene expression profiles and spatial location information were transformed into a gene feature matrix and a cell adjacency matrix. A variational graph autoencoder was then applied to extract features and reduce the dimensions of these two matrices. Following training in the constructed graph neural networks, the latent embeddings of ST data were generated and could be leveraged for spatial domain identification. Through a comparison with established methods, our approach demonstrated superior clustering accuracy. The utilization of accurately segmented spatial regions enables downstream analyses of multiple tumors, encompassing the trajectory of tumor evolution, and facilitating differential gene expression analysis across various cell types.
{"title":"Artificial intelligence enabled spatially resolved transcriptomics reveal spatial tissue organization of multiple tumors","authors":"Teng Liu, Jinxin Ye, Chunnan Hu, Zongbo Zhang, Zhuomiao Ye, Jiangnan Liao, Mingzhu Yin","doi":"10.36922/td.2049","DOIUrl":"https://doi.org/10.36922/td.2049","url":null,"abstract":"Spatially resolved transcriptomics was honored as the Method of the Year 2020 by Nature Methods. This approach allows biologists to precisely discern mRNA expression at the cellular level within structurally preserved tissues. Leveraging artificial intelligence in spatial transcriptomic analysis enhances the understanding of cellular-level biological interactions and offers novel insights into intricate tissues, such as tumor microenvironments. Nevertheless, numerous existing clustering algorithms employing deep learning exhibit the potential for enhancement. In this paper, we focus on graph deep learning-based spatial domain identification for spatial transcriptomics (ST) data from multiple tumors. This identification enables the recognition of cell subpopulations in distinct spatial coordinates, aiding further studies on tumor progression, such as cell-cell communication, pseudo-time trajectory inference, and single-cell deconvolution. Initially, the gene expression profiles and spatial location information were transformed into a gene feature matrix and a cell adjacency matrix. A variational graph autoencoder was then applied to extract features and reduce the dimensions of these two matrices. Following training in the constructed graph neural networks, the latent embeddings of ST data were generated and could be leveraged for spatial domain identification. Through a comparison with established methods, our approach demonstrated superior clustering accuracy. The utilization of accurately segmented spatial regions enables downstream analyses of multiple tumors, encompassing the trajectory of tumor evolution, and facilitating differential gene expression analysis across various cell types.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"141 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140078312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Compressive neuropathies occur when a nerve is compressed in a closed osteofibrous tunnel. Here, we report a case of isolated paralysis of the extensor digitorum longus muscle due to compression of a branch of the posterior interosseous nerve (PIN) in the proximal forearm in a 56-year-old man presented with progressive weakness of the left hand over 18 months. During the first time of clinical consultation, we found a swelling in the extensor aspect of the left proximal forearm, and a firm, non-tender, mobile swelling located deep in the extensor muscles, without other muscle involvement. The sensation was intact. An ultrasound scan and magnetic resonance imaging scan confirmed the diagnosis of an intramuscular lipoma, which was further confirmed with histopathologic examination. The patient was treated with an excision of the lipoma and decompression of the nerve. Post-operatively, the patient was given regular physiotherapy, through which he achieved improvement in his finger extension within a year. This is an extremely rare case of isolated paralysis of the extensor digitorum longus due to compression of the branch of the PIN by an intermuscular lipoma in the forearms.
{"title":"Compressive neuropathy of the branch of the posterior interosseous nerve with isolated paralysis of the extensor digitorum longus muscle: A case report","authors":"Balaji Zacharia, P. K. Pai, Vishnu Unnikrishnan","doi":"10.36922/td.1585","DOIUrl":"https://doi.org/10.36922/td.1585","url":null,"abstract":"Compressive neuropathies occur when a nerve is compressed in a closed osteofibrous tunnel. Here, we report a case of isolated paralysis of the extensor digitorum longus muscle due to compression of a branch of the posterior interosseous nerve (PIN) in the proximal forearm in a 56-year-old man presented with progressive weakness of the left hand over 18 months. During the first time of clinical consultation, we found a swelling in the extensor aspect of the left proximal forearm, and a firm, non-tender, mobile swelling located deep in the extensor muscles, without other muscle involvement. The sensation was intact. An ultrasound scan and magnetic resonance imaging scan confirmed the diagnosis of an intramuscular lipoma, which was further confirmed with histopathologic examination. The patient was treated with an excision of the lipoma and decompression of the nerve. Post-operatively, the patient was given regular physiotherapy, through which he achieved improvement in his finger extension within a year. This is an extremely rare case of isolated paralysis of the extensor digitorum longus due to compression of the branch of the PIN by an intermuscular lipoma in the forearms.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":" 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raul F. Valenzuela, Elvis Duran Sierra, Mathew A. Canjirathinkal, Colleen M. Costelloe, John E. Madewell, William A. Murphy Jr., Behrang Amini
Routine radiologic reporting (RRR) often considers progressive desmoid tumors to have a higher proportion of T2-hyperintense and T1-shortened-enhancing components, while responsive or mature collagenized tumors demonstrate a higher proportion of T2-hypointense-non-enhancing components. We aim to determine the utility of the novel use of contrast-enhanced susceptibility-weighted imaging (CE-SWI) in Desmoid-Tumor treatment response assessment, distinguishing between the T1-shortening-enhancing/T2-hyperintense immature components from the T2-hypointense mature collagenized components. This pilot study included 10 single-lesion extremity desmoid fibromatosis patients undergoing standard-of-care magnetic resonance imaging, including CE-SWI. Three-dimensional (3D) tumor segmentation was performed using MIM software in 48 volumes of interest. Maximum diameter, volume, and modified Choi (mChoi) measurements were computed from CE-SWI and T2-weighted image (T2-WI). Five first-order radiomic features, including mean, skewness, kurtosis, and 10th and 90th percentiles, were calculated using in-house developed software (CARPI-AF). (i) RECIST Progression: We observed two cases of progression according to the T2-WI-based Response Evaluation Criteria in Solid Tumors standard (RECIST). Interestingly, CE-SWI-based-volume and CE-SWI-based-mChoi predicted the same assessment 4.5 months earlier than T2-WI-based-RECIST. RRR assessed both cases as progression; (ii) RECIST Stability: Out of the eight patients classified as having stable disease by T2-WI-based-RECIST, four discrepant progressions were determined: three patients showed an increase greater than 25% of T2-WI-based-volume, and two patients showed an increase greater than 25% of CE-SWI-based-volume. Moreover, from the RECIST stable group, four discrepant-positive responses were predicted by CE-SWI-based-mChoi (three patients) and T2-WI-based-mChoi (four patients). RRR only assessed one patient as having progressive disease; (iii) First-Order Radiomics: CE-SWI detected 23% more 90th-percentile voxels than T2-WI, while T2-WI demonstrated 8.5% more 10th-percentile voxels than CE-SWI. Notably, expected first-order response/progression-related changes in 10th-percentile, 90th-percentile, mean, and skewness were present in 90% of cases. In conclusion, CE-SWI-based-volume and CE-SWI-based-mChoi measurements could improve the prediction of response/progression in desmoid tumors, enhancing the ability in discriminating between T2*- hypointense-collagenized-mature and T1-shortened-enhancing immature components, respectively, in predominant mature responsive and immature progressive tumors, respectively. RRR is relatively insensitive to volumetric tumor changes before RECIST progression and tends to be better tuned with T2* signal and enhancement changes.
{"title":"Early results in the novel use of contrast-enhanced susceptibility-weighted imaging in the assessment of response and progression in desmoid fibromatosis: A pilot study in a specialized cancer institution","authors":"Raul F. Valenzuela, Elvis Duran Sierra, Mathew A. Canjirathinkal, Colleen M. Costelloe, John E. Madewell, William A. Murphy Jr., Behrang Amini","doi":"10.36922/td.1414","DOIUrl":"https://doi.org/10.36922/td.1414","url":null,"abstract":"Routine radiologic reporting (RRR) often considers progressive desmoid tumors to have a higher proportion of T2-hyperintense and T1-shortened-enhancing components, while responsive or mature collagenized tumors demonstrate a higher proportion of T2-hypointense-non-enhancing components. We aim to determine the utility of the novel use of contrast-enhanced susceptibility-weighted imaging (CE-SWI) in Desmoid-Tumor treatment response assessment, distinguishing between the T1-shortening-enhancing/T2-hyperintense immature components from the T2-hypointense mature collagenized components. This pilot study included 10 single-lesion extremity desmoid fibromatosis patients undergoing standard-of-care magnetic resonance imaging, including CE-SWI. Three-dimensional (3D) tumor segmentation was performed using MIM software in 48 volumes of interest. Maximum diameter, volume, and modified Choi (mChoi) measurements were computed from CE-SWI and T2-weighted image (T2-WI). Five first-order radiomic features, including mean, skewness, kurtosis, and 10th and 90th percentiles, were calculated using in-house developed software (CARPI-AF). (i) RECIST Progression: We observed two cases of progression according to the T2-WI-based Response Evaluation Criteria in Solid Tumors standard (RECIST). Interestingly, CE-SWI-based-volume and CE-SWI-based-mChoi predicted the same assessment 4.5 months earlier than T2-WI-based-RECIST. RRR assessed both cases as progression; (ii) RECIST Stability: Out of the eight patients classified as having stable disease by T2-WI-based-RECIST, four discrepant progressions were determined: three patients showed an increase greater than 25% of T2-WI-based-volume, and two patients showed an increase greater than 25% of CE-SWI-based-volume. Moreover, from the RECIST stable group, four discrepant-positive responses were predicted by CE-SWI-based-mChoi (three patients) and T2-WI-based-mChoi (four patients). RRR only assessed one patient as having progressive disease; (iii) First-Order Radiomics: CE-SWI detected 23% more 90th-percentile voxels than T2-WI, while T2-WI demonstrated 8.5% more 10th-percentile voxels than CE-SWI. Notably, expected first-order response/progression-related changes in 10th-percentile, 90th-percentile, mean, and skewness were present in 90% of cases. In conclusion, CE-SWI-based-volume and CE-SWI-based-mChoi measurements could improve the prediction of response/progression in desmoid tumors, enhancing the ability in discriminating between T2*- hypointense-collagenized-mature and T1-shortened-enhancing immature components, respectively, in predominant mature responsive and immature progressive tumors, respectively. RRR is relatively insensitive to volumetric tumor changes before RECIST progression and tends to be better tuned with T2* signal and enhancement changes.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"45 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135634389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The treatment of tumors requires specific and selective drug delivery approaches capable of efficiently eliminating the root cause of oncogenesis. In this context, targeted drug delivery strategies are the preferred choice due to their exceptional recognition of tumor cell biology and their high transfection efficacy within the tumor microenvironment. The emergence of nanoscale techniques has marked significant milestones in the successful management of various types of tumors. The development of targeted delivery approaches for tumor therapeutics has gained momentum over the past few decades. However, in contrast to the plethora of successful pre-clinical studies, only a limited number of passively targeted nanocarriers have been approved for clinical use, and none of the actively targeted nanocarriers have advanced beyond clinical trials. This review delves into the major molecular principles associated with tumorigenesis, including active targeting, passive targeting, and cell-mediated targeting. It also explores the biological barriers (systemic, biological, and cellular) encountered in tumor drug delivery. Moreover, the review examines various tumor-targeted drug delivery systems that have been developed over the past decade. These systems encompass polymeric nanoparticles (micelles, nanoparticles, dendrimers, and polyplexes), lipid-based carriers (solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion), vesicular systems (liposomes, niosomes, aquasomes, and phytosomes), and inorganic nanocarriers (iron oxide nanoparticles, quantum dots, carbon-based nanoparticles, and mesoporous silica nanoparticles), all designed for the alleviation of tumors.
{"title":"Targeted drug delivery approaches for the management of tumors","authors":"Shashi Kiran Misra, Kamla Pathak","doi":"10.36922/td.1356","DOIUrl":"https://doi.org/10.36922/td.1356","url":null,"abstract":"The treatment of tumors requires specific and selective drug delivery approaches capable of efficiently eliminating the root cause of oncogenesis. In this context, targeted drug delivery strategies are the preferred choice due to their exceptional recognition of tumor cell biology and their high transfection efficacy within the tumor microenvironment. The emergence of nanoscale techniques has marked significant milestones in the successful management of various types of tumors. The development of targeted delivery approaches for tumor therapeutics has gained momentum over the past few decades. However, in contrast to the plethora of successful pre-clinical studies, only a limited number of passively targeted nanocarriers have been approved for clinical use, and none of the actively targeted nanocarriers have advanced beyond clinical trials. This review delves into the major molecular principles associated with tumorigenesis, including active targeting, passive targeting, and cell-mediated targeting. It also explores the biological barriers (systemic, biological, and cellular) encountered in tumor drug delivery. Moreover, the review examines various tumor-targeted drug delivery systems that have been developed over the past decade. These systems encompass polymeric nanoparticles (micelles, nanoparticles, dendrimers, and polyplexes), lipid-based carriers (solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion), vesicular systems (liposomes, niosomes, aquasomes, and phytosomes), and inorganic nanocarriers (iron oxide nanoparticles, quantum dots, carbon-based nanoparticles, and mesoporous silica nanoparticles), all designed for the alleviation of tumors.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"93 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135113799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali A Mohamed, Thomas Caussat, Sophie Kelly, Phillip M Johansen, Brandon Lucke-Wold
Choroid plexus tumors (CPT) are believed to originate from outgrowths of the choroid plexus. Despite their broad spectrum of symptoms, invasive nature, and prognosis, most CPTs typically exhibit similar presentations due to their relationship with the cerebral ventricles, as well as the mechanical obstruction and mass effect associated with their growth. In addition, these tumors mainly affect the pediatric population, further complicating the differentiation between benign and malignant subtypes. The World Health Organization classifies CPTs into three grades, namely, grades I, II, or III, based on their mitotic activity, which determine the benign or malignant nature of the tumors. CPTs classified by the World Health Organization (WHO) include choroid plexus papillomas (CPP), atypical CPPs (aCPP), and malignant choroid plexus carcinomas (CPC). Choroid plexus adenomas represent an additional category of benign CPTs not officially classified by the WHO. Despite the variations in histology, immunohistochemistry, imaging, treatment, and prognosis, CPTs cannot be reliably distinguished based solely on clinical presentation. Therefore, in this review, we aim to provide a comprehensive overview of each tumor subtype, along with the current management approach and emerging treatments.
{"title":"Choroid plexus tumors: A spectrum from benign to malignant","authors":"Ali A Mohamed, Thomas Caussat, Sophie Kelly, Phillip M Johansen, Brandon Lucke-Wold","doi":"10.36922/td.1057","DOIUrl":"https://doi.org/10.36922/td.1057","url":null,"abstract":"Choroid plexus tumors (CPT) are believed to originate from outgrowths of the choroid plexus. Despite their broad spectrum of symptoms, invasive nature, and prognosis, most CPTs typically exhibit similar presentations due to their relationship with the cerebral ventricles, as well as the mechanical obstruction and mass effect associated with their growth. In addition, these tumors mainly affect the pediatric population, further complicating the differentiation between benign and malignant subtypes. The World Health Organization classifies CPTs into three grades, namely, grades I, II, or III, based on their mitotic activity, which determine the benign or malignant nature of the tumors. CPTs classified by the World Health Organization (WHO) include choroid plexus papillomas (CPP), atypical CPPs (aCPP), and malignant choroid plexus carcinomas (CPC). Choroid plexus adenomas represent an additional category of benign CPTs not officially classified by the WHO. Despite the variations in histology, immunohistochemistry, imaging, treatment, and prognosis, CPTs cannot be reliably distinguished based solely on clinical presentation. Therefore, in this review, we aim to provide a comprehensive overview of each tumor subtype, along with the current management approach and emerging treatments.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136214685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayushi Mahajan, L. Singh, Gurjeet Singh, R. Dhawan, Manjeet Kaur, P. Malhi, K. Thakur, L. Kaur
Bexarotene is a selective retinoid X receptor agonist of utmost clinical importance. The United States Food and Drug Administration has approved this drug for its effects on cutaneous T-cell lymphoma. Bexarotene has shown great potential, demonstrating enhanced therapeutic activity against a plethora of tumor types, both as a single agent and as an adjuvant with other targeted agents. Despite its potential, bexarotene has turned out to be a nostrum, and formulation-related studies that explore its use have not received much emphasis. Poor aqueous solubility and low bioavailability are challenges in developing an appropriate formulation of this drug. In this review, we aim to provide insights into recent research conducted on formulation development, recent pharmacological findings, patents, and future research requisites of bexarotene, based on the literature gathered from authentic web resources and research articles. Bexarotene is a diamond in the rough, as many researchers have not yet recognized its multipotentiality. The incorporation of bexarotene into nanoformulations can surmount the current drawbacks and efficiently enhance its anticancer activity. In conclusion, this drug is a potentially effective and broad-spectrum anticancer drug for treating malignancies; therefore, extensive research is required to confirm its potential.
{"title":"An evidence-based review on bexarotene","authors":"Ayushi Mahajan, L. Singh, Gurjeet Singh, R. Dhawan, Manjeet Kaur, P. Malhi, K. Thakur, L. Kaur","doi":"10.36922/td.0436","DOIUrl":"https://doi.org/10.36922/td.0436","url":null,"abstract":"Bexarotene is a selective retinoid X receptor agonist of utmost clinical importance. The United States Food and Drug Administration has approved this drug for its effects on cutaneous T-cell lymphoma. Bexarotene has shown great potential, demonstrating enhanced therapeutic activity against a plethora of tumor types, both as a single agent and as an adjuvant with other targeted agents. Despite its potential, bexarotene has turned out to be a nostrum, and formulation-related studies that explore its use have not received much emphasis. Poor aqueous solubility and low bioavailability are challenges in developing an appropriate formulation of this drug. In this review, we aim to provide insights into recent research conducted on formulation development, recent pharmacological findings, patents, and future research requisites of bexarotene, based on the literature gathered from authentic web resources and research articles. Bexarotene is a diamond in the rough, as many researchers have not yet recognized its multipotentiality. The incorporation of bexarotene into nanoformulations can surmount the current drawbacks and efficiently enhance its anticancer activity. In conclusion, this drug is a potentially effective and broad-spectrum anticancer drug for treating malignancies; therefore, extensive research is required to confirm its potential.","PeriodicalId":94260,"journal":{"name":"Tumor discovery","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85187089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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