Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis, and is overexpressed in various cancers. PRAME family proteins are leucine-rich repeat proteins that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcomes in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.
{"title":"Preferentially Expressed Antigen in Melanoma Is a Multifaceted Cancer Testis Antigen with Diverse Roles as a Biomarker and Therapeutic Target","authors":"Mukulika Bose","doi":"10.3390/ijtm3030024","DOIUrl":"https://doi.org/10.3390/ijtm3030024","url":null,"abstract":"Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis, and is overexpressed in various cancers. PRAME family proteins are leucine-rich repeat proteins that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcomes in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86054798","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}
Tsunenori Ouchida, Hiroyuki Suzuki, Tomohiro Tanaka, M. Kaneko, Y. Kato
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab–deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate the developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed anti-mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) via flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) values of H2Mab-300 and H2Mab-304 for CHO/mHER2 were 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD values of H2Mab-300 and H2Mab-304 for NMuMG were 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.
{"title":"Development of Highly Sensitive Anti-Mouse HER2 Monoclonal Antibodies for Flow Cytometry","authors":"Tsunenori Ouchida, Hiroyuki Suzuki, Tomohiro Tanaka, M. Kaneko, Y. Kato","doi":"10.3390/ijtm3030022","DOIUrl":"https://doi.org/10.3390/ijtm3030022","url":null,"abstract":"Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab–deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate the developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed anti-mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) via flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) values of H2Mab-300 and H2Mab-304 for CHO/mHER2 were 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD values of H2Mab-300 and H2Mab-304 for NMuMG were 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91044277","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}
C. Kohchi, Miyuki Uehiro, Masashi Yamashita, H. Inagawa, G. Soma
In this study, the effects of foods containing lipopolysaccharide (LPS) from Pantoea agglomerans (LPSp) on immunity were preliminarily investigated using a double-blind, placebo-controlled, randomized, parallel-group comparative study design. Thirty healthy subjects aged ≥ 20 years (four males and twenty-six females; mean age 49 ± 9.2 years) were randomly assigned to the LPS-containing food group (488 μg/day; LPS) or placebo group. Each food was consumed for 8 weeks, and a subjective survey of cold symptoms (Wisconsin Upper Respiratory Symptom Questionnaire) and allergic symptoms of the eyes and nose were conducted. Phagocytic capacity and lymphocyte counts were measured as indicators of immune function. There were no significant between-group differences with respect to any of the investigated items. On sub-group analysis of eye–nose allergy symptom score, confined only to subjects who reported eye–nose allergic symptoms in previous years, the LPS group showed a trend toward milder symptoms compared to the placebo group. In addition, when the symptom scores were compared only for subjects who developed eye–nose allergies during the study period, the LPS group showed significantly lower overall scores and eye symptom scores compared to the placebo group. These results suggest that the consumption of LPS-containing foods may alleviate or prevent eye–nose allergies. There were no statistically predominant changes in hematology and blood biochemistry tests, indicating that continued consumption of LPS-containing foods is safe. (UMIN000046154).
{"title":"Foods Containing Pantoea agglomerans LPS Reduce Eye-Nose Allergies—A Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Comparative Pilot Study","authors":"C. Kohchi, Miyuki Uehiro, Masashi Yamashita, H. Inagawa, G. Soma","doi":"10.3390/ijtm3030021","DOIUrl":"https://doi.org/10.3390/ijtm3030021","url":null,"abstract":"In this study, the effects of foods containing lipopolysaccharide (LPS) from Pantoea agglomerans (LPSp) on immunity were preliminarily investigated using a double-blind, placebo-controlled, randomized, parallel-group comparative study design. Thirty healthy subjects aged ≥ 20 years (four males and twenty-six females; mean age 49 ± 9.2 years) were randomly assigned to the LPS-containing food group (488 μg/day; LPS) or placebo group. Each food was consumed for 8 weeks, and a subjective survey of cold symptoms (Wisconsin Upper Respiratory Symptom Questionnaire) and allergic symptoms of the eyes and nose were conducted. Phagocytic capacity and lymphocyte counts were measured as indicators of immune function. There were no significant between-group differences with respect to any of the investigated items. On sub-group analysis of eye–nose allergy symptom score, confined only to subjects who reported eye–nose allergic symptoms in previous years, the LPS group showed a trend toward milder symptoms compared to the placebo group. In addition, when the symptom scores were compared only for subjects who developed eye–nose allergies during the study period, the LPS group showed significantly lower overall scores and eye symptom scores compared to the placebo group. These results suggest that the consumption of LPS-containing foods may alleviate or prevent eye–nose allergies. There were no statistically predominant changes in hematology and blood biochemistry tests, indicating that continued consumption of LPS-containing foods is safe. (UMIN000046154).","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74861731","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}
Shaila Cejudo-Arteaga, Marco Antonio Ramírez-Reyes, M. A. Badillo-Santoyo, E. Martínez-Cordero, Felipe Farías-Serratos, M. Maldonado-Vega
Androgen deprivation therapy (ADT) is the basis for the control of prostate cancer. High levels of prostate-specific antigen (PSA) and high Gleason grade correlate, define the aggressiveness of the cancer in order to establish its treatment and prognosis. This work evaluated the response of 910 patients diagnosed with prostate cancer, separated into three groups according to their response to treatment by ADT: (1) sensitive (TSPC); (2) palliative and did not accept treatment, and (3) group with recurrence or treatment resistance (TRPC). All patients with prostate cancer treated with ADT, and regardless of whether or not they had undergone surgery or taken to radiotherapy, presented with anemia. The hematological response due to the leukocyte/lymphocyte index (L/L) is increased at the end of treatment, possibly due to inflammatory processes generated by cancer, and baseline overweight and obesity. Patients with biochemical relapse exhibit a higher platelet count, suggesting that these cells could participate in the recurrence process and in metastasis (78%) in these patients. The coagulation index (INR) could be an indicator of the platelet response to be considered during the treatment and monitoring of patients.
{"title":"Prostate Cancer, Treatment and Response of the Hematological System in Mexican Population","authors":"Shaila Cejudo-Arteaga, Marco Antonio Ramírez-Reyes, M. A. Badillo-Santoyo, E. Martínez-Cordero, Felipe Farías-Serratos, M. Maldonado-Vega","doi":"10.3390/ijtm3030020","DOIUrl":"https://doi.org/10.3390/ijtm3030020","url":null,"abstract":"Androgen deprivation therapy (ADT) is the basis for the control of prostate cancer. High levels of prostate-specific antigen (PSA) and high Gleason grade correlate, define the aggressiveness of the cancer in order to establish its treatment and prognosis. This work evaluated the response of 910 patients diagnosed with prostate cancer, separated into three groups according to their response to treatment by ADT: (1) sensitive (TSPC); (2) palliative and did not accept treatment, and (3) group with recurrence or treatment resistance (TRPC). All patients with prostate cancer treated with ADT, and regardless of whether or not they had undergone surgery or taken to radiotherapy, presented with anemia. The hematological response due to the leukocyte/lymphocyte index (L/L) is increased at the end of treatment, possibly due to inflammatory processes generated by cancer, and baseline overweight and obesity. Patients with biochemical relapse exhibit a higher platelet count, suggesting that these cells could participate in the recurrence process and in metastasis (78%) in these patients. The coagulation index (INR) could be an indicator of the platelet response to be considered during the treatment and monitoring of patients.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81531733","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}
R. De Wilde, Michael Saerens, A. Hoorens, A. Geerts, C. Jacobs
Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH.
{"title":"Treatment of Refractory Checkpoint-Inhibitor-Induced Hepatitis with Tacrolimus: A Case and Review of the Literature","authors":"R. De Wilde, Michael Saerens, A. Hoorens, A. Geerts, C. Jacobs","doi":"10.3390/ijtm3030019","DOIUrl":"https://doi.org/10.3390/ijtm3030019","url":null,"abstract":"Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81846162","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}
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a significant impact on the world’s demographics, resulting in over 6 million deaths globally. COVID-19 has been associated with a variety of disease manifestations in various organ systems, including kidney disease, in addition to pulmonary manifestations. Infection with SARS-CoV-2 can not only cause new kidney damage but also make treatment and care more difficult, as well as increase mortality in people who already have kidney problems. COVID-19 is indeed associated with a variety of renal pathologies, such as acute tubular necrosis, proteinuria, hematuria, and thrombosis complications. Cytokine storms, hypoxemia, direct viral invasion via angiotensin-converting enzyme 2 and cathepsin L, electrolyte imbalance, and fever are among the pathophysiological mechanisms underlying these clinical symptoms. Over the last two years, many COVID-19 vaccines have been discovered. However, there have been a few case reports of AKI, AKD, proteinuria, edema, gross hematuria, and other renal side effects that necessitated hospitalization after receiving COVID-19 vaccinations. Thus, the current review aimed to evaluate COVID-19-induced kidney dysfunction in terms of clinical features, pathogenesis, long-term outcomes, and vaccine harms based on the most up-to-date findings.
{"title":"Insights into COVID-19 and Its Potential Implications for Kidney Dysfunction","authors":"A. Abdel-Moneim, Eman H. Bakry, M. Zaky","doi":"10.3390/ijtm3020018","DOIUrl":"https://doi.org/10.3390/ijtm3020018","url":null,"abstract":"Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a significant impact on the world’s demographics, resulting in over 6 million deaths globally. COVID-19 has been associated with a variety of disease manifestations in various organ systems, including kidney disease, in addition to pulmonary manifestations. Infection with SARS-CoV-2 can not only cause new kidney damage but also make treatment and care more difficult, as well as increase mortality in people who already have kidney problems. COVID-19 is indeed associated with a variety of renal pathologies, such as acute tubular necrosis, proteinuria, hematuria, and thrombosis complications. Cytokine storms, hypoxemia, direct viral invasion via angiotensin-converting enzyme 2 and cathepsin L, electrolyte imbalance, and fever are among the pathophysiological mechanisms underlying these clinical symptoms. Over the last two years, many COVID-19 vaccines have been discovered. However, there have been a few case reports of AKI, AKD, proteinuria, edema, gross hematuria, and other renal side effects that necessitated hospitalization after receiving COVID-19 vaccinations. Thus, the current review aimed to evaluate COVID-19-induced kidney dysfunction in terms of clinical features, pathogenesis, long-term outcomes, and vaccine harms based on the most up-to-date findings.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74821701","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}
Francesco Bruno, Paolo Abondio, Valentina Laganà, R. Colao, S. Curcio, F. Frangipane, G. Puccio, R. D. Di Lorenzo, A. Bruni, R. Maletta
Older adults with dementia present an increased risk of mortality due to seasonal influenza. Despite concerning evidence, the influenza vaccination program has been unsuccessful, with low rates of uptake in Italian people ≥65 years. In addition, being vaccinated does not eliminate the risk of contracting a virus, especially by coming into close contact with other possibly unvaccinated people, such as family caregivers in the home environment. Therefore, the refusal of family caregivers to get vaccinated for seasonal influenza could have dire consequences for their relatives with dementia. The aims of this study were to investigate the predictive role of the Theory of Planned Behavior model (TPB) and past vaccination behavior on the intention to receive a seasonal influenza vaccine among family caregivers of people with dementia. Data were collected from seventy-one respondents during July–September 2021 using a cross-sectional web-based survey design. Results of hierarchical binary logistic regression showed that TPB (i.e., attitudes towards vaccination, subjective norms, and perceived behavioral control) explained 51.6% of the variance in intention to receive a seasonal influenza vaccine; past vaccination behavior increased this to 58.8%. In conclusion, past vaccination behavior and the theory of planned behavior variables effectively predict influenza vaccine willingness of family caregivers of people with dementia and should be targeted in vaccination campaigns.
{"title":"Using the Theory of Planned Behavior and Past Behavior to Explain the Intention to Receive a Seasonal Influenza Vaccine among Family Caregivers of People with Dementia","authors":"Francesco Bruno, Paolo Abondio, Valentina Laganà, R. Colao, S. Curcio, F. Frangipane, G. Puccio, R. D. Di Lorenzo, A. Bruni, R. Maletta","doi":"10.3390/ijtm3020017","DOIUrl":"https://doi.org/10.3390/ijtm3020017","url":null,"abstract":"Older adults with dementia present an increased risk of mortality due to seasonal influenza. Despite concerning evidence, the influenza vaccination program has been unsuccessful, with low rates of uptake in Italian people ≥65 years. In addition, being vaccinated does not eliminate the risk of contracting a virus, especially by coming into close contact with other possibly unvaccinated people, such as family caregivers in the home environment. Therefore, the refusal of family caregivers to get vaccinated for seasonal influenza could have dire consequences for their relatives with dementia. The aims of this study were to investigate the predictive role of the Theory of Planned Behavior model (TPB) and past vaccination behavior on the intention to receive a seasonal influenza vaccine among family caregivers of people with dementia. Data were collected from seventy-one respondents during July–September 2021 using a cross-sectional web-based survey design. Results of hierarchical binary logistic regression showed that TPB (i.e., attitudes towards vaccination, subjective norms, and perceived behavioral control) explained 51.6% of the variance in intention to receive a seasonal influenza vaccine; past vaccination behavior increased this to 58.8%. In conclusion, past vaccination behavior and the theory of planned behavior variables effectively predict influenza vaccine willingness of family caregivers of people with dementia and should be targeted in vaccination campaigns.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89406751","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}
Viren Soni, Dr Akhil Nagar, Ruchita Bardiya, Jacob Mara, Lukas Von Suskil, Sabrina Rose, Chetan Sonawane
Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. Here we point out the noteworthy work reported on SAL’s mechanism of action, anticancer activities, toxicity, and clinic applications. In addition, SAL derivatives synthesized by different research groups and their biological activity will also be highlighted.
{"title":"A Concise Review of Prodigious Salinomycin and Its Derivatives Effective in Treatment of Breast Cancer: (2012–2022)","authors":"Viren Soni, Dr Akhil Nagar, Ruchita Bardiya, Jacob Mara, Lukas Von Suskil, Sabrina Rose, Chetan Sonawane","doi":"10.3390/ijtm3020016","DOIUrl":"https://doi.org/10.3390/ijtm3020016","url":null,"abstract":"Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. Here we point out the noteworthy work reported on SAL’s mechanism of action, anticancer activities, toxicity, and clinic applications. In addition, SAL derivatives synthesized by different research groups and their biological activity will also be highlighted.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75152306","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}
V. Giardini, C. Gambacorti-Passerini, M. Casati, Andrea Carrer, P. Vergani
Preeclampsia is an obstetric pathology with striking similarities to COVID-19. The renin-angiotensin system plays a key role in the pathogenesis of both diseases. This report reviews the pharmacological strategies that have been suggested for the prevention and treatment of preeclampsia and that are potentially useful also in the treatment of COVID-19. Of note, both pathologies have in common an Angiotensin II-mediated endothelial dysfunction secondary to an angiogenic imbalance, with effects on vasculature, coagulation, and inflammation. These considerations are drawn from cases of the initial SARS-CoV-2 primary infection and may not apply to more recent SARS-CoV-2 variants or infections after COVID vaccination. The treatment options discussed included albumin infusion, aspirin, corticosteroids, the monoclonal antibody eculizumab, hydroxychloroquine, low molecular weight heparin, magnesium, melatonin, metformin, nitric oxide, proton pump inhibitors, statins, therapeutic apheresis, and vitamin D.
{"title":"Analogies between COVID-19 and Preeclampsia: Focus on Therapies","authors":"V. Giardini, C. Gambacorti-Passerini, M. Casati, Andrea Carrer, P. Vergani","doi":"10.3390/ijtm3020015","DOIUrl":"https://doi.org/10.3390/ijtm3020015","url":null,"abstract":"Preeclampsia is an obstetric pathology with striking similarities to COVID-19. The renin-angiotensin system plays a key role in the pathogenesis of both diseases. This report reviews the pharmacological strategies that have been suggested for the prevention and treatment of preeclampsia and that are potentially useful also in the treatment of COVID-19. Of note, both pathologies have in common an Angiotensin II-mediated endothelial dysfunction secondary to an angiogenic imbalance, with effects on vasculature, coagulation, and inflammation. These considerations are drawn from cases of the initial SARS-CoV-2 primary infection and may not apply to more recent SARS-CoV-2 variants or infections after COVID vaccination. The treatment options discussed included albumin infusion, aspirin, corticosteroids, the monoclonal antibody eculizumab, hydroxychloroquine, low molecular weight heparin, magnesium, melatonin, metformin, nitric oxide, proton pump inhibitors, statins, therapeutic apheresis, and vitamin D.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79090685","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}
Malaria and HIV are geographically in the tropics and subtropics of the world, including sub-Saharan Africa. Understanding the overlapping effect of both infections, especially among pregnant women, is crucial in managing pregnant women during antenatal care visits, and postpartum babies. It was realized that the prevalence of malaria among HIV-positive pregnant women ranges between 31–61%, while for non-HIV infected pregnant women the prevalence still stands between 10 and 36%. Co-infection is between 0.52 and 56.3%. Even though the rate of mother-to-child transmission of HIV has dropped, MTCT of malaria still remains a problem. MTCT is associated with low birth-weight, anemia, and even immune dysregulation. The adoption of the Option B+ plan has proven to be effective in the fight against the MTCT of HIV. However, malaria in pregnancy still remains a problem. Concurrent administration of both antimalarial drugs and Cotrimozaxole to pregnant women is not recommended, because of the toxic effect of the interaction of both drugs. Nevertheless, studies looking at the effect of the current ART regimens on mothers and their children need to be carried out. Studies looking at exposed children over a longer period of time, to determine their susceptibility to malaria infection and also to monitor their immune response to malaria over time, are needed.
{"title":"Malaria and HIV Co-Infection among Pregnant Women in Africa: Prevalence, Effect on Immunity and Clinical Management: Review","authors":"B. Obase, J. Bigoga, D. Nsagha","doi":"10.3390/ijtm3020014","DOIUrl":"https://doi.org/10.3390/ijtm3020014","url":null,"abstract":"Malaria and HIV are geographically in the tropics and subtropics of the world, including sub-Saharan Africa. Understanding the overlapping effect of both infections, especially among pregnant women, is crucial in managing pregnant women during antenatal care visits, and postpartum babies. It was realized that the prevalence of malaria among HIV-positive pregnant women ranges between 31–61%, while for non-HIV infected pregnant women the prevalence still stands between 10 and 36%. Co-infection is between 0.52 and 56.3%. Even though the rate of mother-to-child transmission of HIV has dropped, MTCT of malaria still remains a problem. MTCT is associated with low birth-weight, anemia, and even immune dysregulation. The adoption of the Option B+ plan has proven to be effective in the fight against the MTCT of HIV. However, malaria in pregnancy still remains a problem. Concurrent administration of both antimalarial drugs and Cotrimozaxole to pregnant women is not recommended, because of the toxic effect of the interaction of both drugs. Nevertheless, studies looking at the effect of the current ART regimens on mothers and their children need to be carried out. Studies looking at exposed children over a longer period of time, to determine their susceptibility to malaria infection and also to monitor their immune response to malaria over time, are needed.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78852209","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}