Pub Date : 2022-05-14DOI: 10.17305/bjbms.2022.7147
A. Topçu, A. Ozturk, I. Yurtsever, M. Besiroglu, A. I. Yasin, H. Turk, M. Seker
Erlotinib, a tyrosine kinase inhibitor, has been shown to improve the survival of patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Sarcopenia is a status with increasing importance in lung cancer, and it may predict a poor prognosis. We aimed to evaluate the impact of sarcopenia on erlotinib therapy and prognosis in patients with EGFR-mutated (exon 19 or 21 L858R) metastatic lung adenocarcinoma. Sarcopenia was defined as skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men. The patient characteristics, inflammation parameters, clinical and survival outcomes of the erlotinib therapy were examined according to sarcopenia status. We also analyzed the erlotinib treatment-related toxicity. Seventy-two patients were included in our retrospective study, and the mean age of the patients was 63.7 years. A total of 39 (54.2%) patients were diagnosed with sarcopenia. Patients with sarcopenia had a poor prognosis and had a shorter median progression-free survival (PFS) than patients without sarcopenia (10.5 months vs. 21.8 months, p = 0.002). Sarcopenia (HR 2.08) and C-reactive protein > 6.5 mg/L (HR 2.57) were determined as independent poor prognostic factors for PFS of erlotinib therapy. Treatment-related toxicity occurred in 34.7% of patients treated with erlotinib, and sarcopenia did not significantly affect treatment-related toxicity. We also found that sarcopenia significantly affected the response to erlotinib. The expected survival outcomes may be low when erlotinib therapy is used in patients with sarcopenia and metastatic lung adenocarcinoma. This study showed that survival and clinical outcomes could be better predicted by detecting sarcopenia in patients with lung cancer using erlotinib.
{"title":"The effect of sarcopenia on erlotinib therapy in patients with metastatic lung adenocarcinoma","authors":"A. Topçu, A. Ozturk, I. Yurtsever, M. Besiroglu, A. I. Yasin, H. Turk, M. Seker","doi":"10.17305/bjbms.2022.7147","DOIUrl":"https://doi.org/10.17305/bjbms.2022.7147","url":null,"abstract":"Erlotinib, a tyrosine kinase inhibitor, has been shown to improve the survival of patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Sarcopenia is a status with increasing importance in lung cancer, and it may predict a poor prognosis. We aimed to evaluate the impact of sarcopenia on erlotinib therapy and prognosis in patients with EGFR-mutated (exon 19 or 21 L858R) metastatic lung adenocarcinoma. Sarcopenia was defined as skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men. The patient characteristics, inflammation parameters, clinical and survival outcomes of the erlotinib therapy were examined according to sarcopenia status. We also analyzed the erlotinib treatment-related toxicity. Seventy-two patients were included in our retrospective study, and the mean age of the patients was 63.7 years. A total of 39 (54.2%) patients were diagnosed with sarcopenia. Patients with sarcopenia had a poor prognosis and had a shorter median progression-free survival (PFS) than patients without sarcopenia (10.5 months vs. 21.8 months, p = 0.002). Sarcopenia (HR 2.08) and C-reactive protein > 6.5 mg/L (HR 2.57) were determined as independent poor prognostic factors for PFS of erlotinib therapy. Treatment-related toxicity occurred in 34.7% of patients treated with erlotinib, and sarcopenia did not significantly affect treatment-related toxicity. We also found that sarcopenia significantly affected the response to erlotinib. The expected survival outcomes may be low when erlotinib therapy is used in patients with sarcopenia and metastatic lung adenocarcinoma. This study showed that survival and clinical outcomes could be better predicted by detecting sarcopenia in patients with lung cancer using erlotinib.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"982 - 991"},"PeriodicalIF":3.4,"publicationDate":"2022-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67671021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-30DOI: 10.17305/bjbms.2021.6704
Peng Hua, D. Yang, Ruie Chen, P. Qiu, Meiwan Chen
Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.
{"title":"ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity","authors":"Peng Hua, D. Yang, Ruie Chen, P. Qiu, Meiwan Chen","doi":"10.17305/bjbms.2021.6704","DOIUrl":"https://doi.org/10.17305/bjbms.2021.6704","url":null,"abstract":"Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"176 3","pages":"593 - 607"},"PeriodicalIF":3.4,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41255693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-29DOI: 10.17305/bjbms.2021.7225
Silvia Mariani, M. D. De Piero, Justine M. Ravaux, Alexander Saelmans, Michal J Kawczynski, B. V. van Bussel, Michele Di Mauro, A. Willers, J. Swol, M. Kowalewski, Tong Li, T. Delnoij, I. V. D. van der Horst, Jos Maessen, R. Lorusso
The regenerative potential of cardiomyocytes in adult mammals is limited. The previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury.
{"title":"LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis","authors":"Silvia Mariani, M. D. De Piero, Justine M. Ravaux, Alexander Saelmans, Michal J Kawczynski, B. V. van Bussel, Michele Di Mauro, A. Willers, J. Swol, M. Kowalewski, Tong Li, T. Delnoij, I. V. D. van der Horst, Jos Maessen, R. Lorusso","doi":"10.17305/bjbms.2021.7225","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7225","url":null,"abstract":"The regenerative potential of cardiomyocytes in adult mammals is limited. The previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"772 - 783"},"PeriodicalIF":3.4,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45573964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-17DOI: 10.17305/bjbms.2021.7069
S. Aktürk Esen, Y. Ergun, C. Erol, R. Arıkan, M. Er, M. Atçı, A. Topçu, G. Ucar, Baran Akagündüz, M. Aykan, M. Özen, N. K. Baytemur, Melike Özçelik, E. Şahin, D. Güven, S. Menekşe, N. Ak, F. Teker, E. Kut, T. Şakalar, Özkan Alan, T. Kaçan, N. Turhal, S. Kılıçkap, S. Türker, M. Şendur, Osman Köstek, M. Karaağaç, A. Sakin, H. M. Türk, D. Çağlayan, Ş. Cihan, Y. Açıkgöz, D. Uncu
Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (p = 0.495). About 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (p = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, p = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, p = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.
{"title":"First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer","authors":"S. Aktürk Esen, Y. Ergun, C. Erol, R. Arıkan, M. Er, M. Atçı, A. Topçu, G. Ucar, Baran Akagündüz, M. Aykan, M. Özen, N. K. Baytemur, Melike Özçelik, E. Şahin, D. Güven, S. Menekşe, N. Ak, F. Teker, E. Kut, T. Şakalar, Özkan Alan, T. Kaçan, N. Turhal, S. Kılıçkap, S. Türker, M. Şendur, Osman Köstek, M. Karaağaç, A. Sakin, H. M. Türk, D. Çağlayan, Ş. Cihan, Y. Açıkgöz, D. Uncu","doi":"10.17305/bjbms.2021.7069","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7069","url":null,"abstract":"Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (p = 0.495). About 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (p = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, p = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, p = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"818 - 825"},"PeriodicalIF":3.4,"publicationDate":"2022-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49142080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ameliorative effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonists have been demonstrated in acute kidney injury (AKI) caused by multiple stimulations. However, the ameliorative effect of α7nAChR on sepsis-induced AKI (SAKI) in the cecal ligation and puncture (CLP) model is unclear. The previous studies have demonstrated that α7nAChR is highly expressed on the surface of CD4+CD25+ regulatory T cells (Tregs). However, the role of Tregs in SAKI is unclear. We hypothesized that Tregs might play a role in the ameliorative effect of α7nAChR on SAKI. Hence, in this study, we determined the effects of PNU-282987 (a selective α7nAchR agonist) on SAKI and evaluated whether PNU-282987 would attenuate SAKI through regulating Tregs. Our study showed that immediate administration of PNU-282987 after CLP surgery in rats improved renal function, reduced levels of systemic inflammatory factors (tumor necrosis factor-α, interleukin-6, etc.), inflammatory cell infiltration and tubular apoptosis in renal tissues, and increased forkhead/winged helix transcription factor p3 (Foxp3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression indicating activated Tregs. Moreover, in in vitro experiments, isolated Tregs cocultured with PNU-282987 also displayed enhanced expression of CTLA-4 and Foxp3. Furthermore, Tregs were cocultured with PNU-282987 for 24 hours and then reinfused into rats through the tail vein immediately after CLP surgery, and a significant renal protective effect was observed 24 hours postoperatively. These results demonstrate that PNU-282987 exerts its renal protective effects on SAKI through activation of Tregs.
{"title":"The α7 nicotinic acetylcholine receptor agonist PNU-282987 ameliorates sepsis-induced acute kidney injury through CD4+CD25+ regulatory T cells in rats","authors":"Xiaocui Shi, Juncong Li, Yuzhen Han, Jingyi Wang, Qingping Li, Yue Zheng, Wenxiong Li","doi":"10.17305/bjbms.2022.7111","DOIUrl":"https://doi.org/10.17305/bjbms.2022.7111","url":null,"abstract":"The ameliorative effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonists have been demonstrated in acute kidney injury (AKI) caused by multiple stimulations. However, the ameliorative effect of α7nAChR on sepsis-induced AKI (SAKI) in the cecal ligation and puncture (CLP) model is unclear. The previous studies have demonstrated that α7nAChR is highly expressed on the surface of CD4+CD25+ regulatory T cells (Tregs). However, the role of Tregs in SAKI is unclear. We hypothesized that Tregs might play a role in the ameliorative effect of α7nAChR on SAKI. Hence, in this study, we determined the effects of PNU-282987 (a selective α7nAchR agonist) on SAKI and evaluated whether PNU-282987 would attenuate SAKI through regulating Tregs. Our study showed that immediate administration of PNU-282987 after CLP surgery in rats improved renal function, reduced levels of systemic inflammatory factors (tumor necrosis factor-α, interleukin-6, etc.), inflammatory cell infiltration and tubular apoptosis in renal tissues, and increased forkhead/winged helix transcription factor p3 (Foxp3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression indicating activated Tregs. Moreover, in in vitro experiments, isolated Tregs cocultured with PNU-282987 also displayed enhanced expression of CTLA-4 and Foxp3. Furthermore, Tregs were cocultured with PNU-282987 for 24 hours and then reinfused into rats through the tail vein immediately after CLP surgery, and a significant renal protective effect was observed 24 hours postoperatively. These results demonstrate that PNU-282987 exerts its renal protective effects on SAKI through activation of Tregs.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"882 - 893"},"PeriodicalIF":3.4,"publicationDate":"2022-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42635272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-08DOI: 10.17305/bjbms.2021.7134
T. Cerić, E. Sokolović, A. Pašić, Emina Borovac-Gurda, Velda Smajlbegović, Berisa Hasanbegović, Emina Bičakčić Filipović, Elma Kapisazović, Selma Sokolović, S. Bešlija
The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-CoV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to complete an individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.
{"title":"Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: A single-center cross-sectional study","authors":"T. Cerić, E. Sokolović, A. Pašić, Emina Borovac-Gurda, Velda Smajlbegović, Berisa Hasanbegović, Emina Bičakčić Filipović, Elma Kapisazović, Selma Sokolović, S. Bešlija","doi":"10.17305/bjbms.2021.7134","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7134","url":null,"abstract":"The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-CoV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to complete an individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"833 - 842"},"PeriodicalIF":3.4,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47834257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-03DOI: 10.17305/bjbms.2021.7082
Hanyan Meng, Jian-hua Mao, Qing Ye
The first-generation SARS-CoV-2 vaccines have played a significant role in controlling the COVID-19 pandemic, preventing severe diseases, and reducing mortality. However, the continuous emergence of SARS-CoV-2 variants, the persistence of breakthrough infections, and the seemingly rapid decline in the protective efficacy of SARS-CoV-2 vaccines have presented additional challenges for the next phase. There is an urgent need to confirm the necessity of further booster vaccination and combination vaccine approaches. This paper summarizes the latest literature on SARS-CoV-2 variants and vaccine effectiveness and concludes that it is essential to implement booster immunization strategies. Priority should be given to high-risk groups, the elderly, and immunocompromised people. In addition, heterologous vaccination has a longer duration of effect and a broader spectrum than homologous vaccination, making it more conducive to managing the immune escape of SARS-CoV-2 variants.
{"title":"Strategies and safety considerations of booster vaccination in COVID-19","authors":"Hanyan Meng, Jian-hua Mao, Qing Ye","doi":"10.17305/bjbms.2021.7082","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7082","url":null,"abstract":"The first-generation SARS-CoV-2 vaccines have played a significant role in controlling the COVID-19 pandemic, preventing severe diseases, and reducing mortality. However, the continuous emergence of SARS-CoV-2 variants, the persistence of breakthrough infections, and the seemingly rapid decline in the protective efficacy of SARS-CoV-2 vaccines have presented additional challenges for the next phase. There is an urgent need to confirm the necessity of further booster vaccination and combination vaccine approaches. This paper summarizes the latest literature on SARS-CoV-2 variants and vaccine effectiveness and concludes that it is essential to implement booster immunization strategies. Priority should be given to high-risk groups, the elderly, and immunocompromised people. In addition, heterologous vaccination has a longer duration of effect and a broader spectrum than homologous vaccination, making it more conducive to managing the immune escape of SARS-CoV-2 variants.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"366 - 373"},"PeriodicalIF":3.4,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41828093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-02DOI: 10.17305/bjbms.2021.7019
Fang Qian, Wei Kong, Shuaiqun Wang
Recent studies have shown that different signaling pathways are involved in the pathogenesis of Alzheimer’s disease (AD), with complex molecular connections existing between these pathways. Autophagy is crucial for the degradation and production of pathogenic proteins in AD, and it shows link with other AD-related pathways. However, the current methods for identifying potential therapeutic targets for AD are primarily based on single-gene analysis or a single signal pathway, both of which are somewhat limited. Finding other methods are necessary for providing novel underlying AD therapeutic targets. Therefore, given the central role of autophagy in AD and its interplay with its pathways, we aimed to identify prognostic genes related to autophagy within and between these pathways based on pathway crosstalk analysis. The method of pathway analysis based on global influence was applied to find the feature mRNAs involved in the crosstalk between autophagy and other AD-related pathways. Subsequently, the weighted gene coexpression network analysis was used to construct a coexpression module of feature mRNAs and differential long non-coding RNAs. Finally, based on two autophagy-related crosstalk genes (CD40 and SMAD7), we constructed a prognosis model by multivariate Cox regression, which could predict the overall survival of AD patients with medium-to-high accuracy. In conclusion, we provided an effective method for extracting autophagy-related significant genes based on pathway crosstalk in AD. We found the biomarkers valuable to the AD prognosis, which may also play an essential role in the development and treatment of AD.
{"title":"Exploring autophagy-related prognostic genes of Alzheimer’s disease based on pathway crosstalk analysis","authors":"Fang Qian, Wei Kong, Shuaiqun Wang","doi":"10.17305/bjbms.2021.7019","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7019","url":null,"abstract":"Recent studies have shown that different signaling pathways are involved in the pathogenesis of Alzheimer’s disease (AD), with complex molecular connections existing between these pathways. Autophagy is crucial for the degradation and production of pathogenic proteins in AD, and it shows link with other AD-related pathways. However, the current methods for identifying potential therapeutic targets for AD are primarily based on single-gene analysis or a single signal pathway, both of which are somewhat limited. Finding other methods are necessary for providing novel underlying AD therapeutic targets. Therefore, given the central role of autophagy in AD and its interplay with its pathways, we aimed to identify prognostic genes related to autophagy within and between these pathways based on pathway crosstalk analysis. The method of pathway analysis based on global influence was applied to find the feature mRNAs involved in the crosstalk between autophagy and other AD-related pathways. Subsequently, the weighted gene coexpression network analysis was used to construct a coexpression module of feature mRNAs and differential long non-coding RNAs. Finally, based on two autophagy-related crosstalk genes (CD40 and SMAD7), we constructed a prognosis model by multivariate Cox regression, which could predict the overall survival of AD patients with medium-to-high accuracy. In conclusion, we provided an effective method for extracting autophagy-related significant genes based on pathway crosstalk in AD. We found the biomarkers valuable to the AD prognosis, which may also play an essential role in the development and treatment of AD.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"751 - 771"},"PeriodicalIF":3.4,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43350116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.17305/bjbms.2021.5879
Pinli Zou, Min Zhou, Jinquan Wen, Xin Liao, Yali Shen, Haiyan Liu, Lin Song, Jianwen Xiao
Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.
{"title":"The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers.","authors":"Pinli Zou, Min Zhou, Jinquan Wen, Xin Liao, Yali Shen, Haiyan Liu, Lin Song, Jianwen Xiao","doi":"10.17305/bjbms.2021.5879","DOIUrl":"https://doi.org/10.17305/bjbms.2021.5879","url":null,"abstract":"<p><p>Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 2","pages":"238-246"},"PeriodicalIF":3.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39311508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.17305/bjbms.2021.6419
Zhe-Sheng Chen, Dong-Hua Yang
The therapeutic modalities of early-stage and advanced extranodal natural killer/T-cell lymphoma (NKTCL) patients are completely different. The former is mainly radiotherapy with or without chemotherapy, while the latter relies on chemotherapy-based systemic treatment.1,2 According to Ann Arbor staging system, approximately 70% of the NKTCL patients are classified as early-stage cases who are promising to be cured.3 Considering NKTCL is sensitive to radiation but may be resistant to chemotherapy, the radiotherapy is considered to be the most important treatment for some early-stage patients with a satisfactory local control rate and could be used alone.4 However, systemic recurrence after radiotherapy in a portion of NKTCL patients seriously affects their long-term survival, and the first-line treatment combined with radiotherapy and chemotherapy is considered necessary. Therefore, the use of radiotherapy alone in early-stage NKTCL is still a controversial issue.5,6 Read more in PDF.
{"title":"Selection of optimal therapeutic modality for early-stage extranodal natural killer/T-cell lymphoma patients under the guidance of single-nucleotide polymorphism signature.","authors":"Zhe-Sheng Chen, Dong-Hua Yang","doi":"10.17305/bjbms.2021.6419","DOIUrl":"https://doi.org/10.17305/bjbms.2021.6419","url":null,"abstract":"The therapeutic modalities of early-stage and advanced extranodal natural killer/T-cell lymphoma (NKTCL) patients are completely different. The former is mainly radiotherapy with or without chemotherapy, while the latter relies on chemotherapy-based systemic treatment.1,2 According to Ann Arbor staging system, approximately 70% of the NKTCL patients are classified as early-stage cases who are promising to be cured.3 Considering NKTCL is sensitive to radiation but may be resistant to chemotherapy, the radiotherapy is considered to be the most important treatment for some early-stage patients with a satisfactory local control rate and could be used alone.4 However, systemic recurrence after radiotherapy in a portion of NKTCL patients seriously affects their long-term survival, and the first-line treatment combined with radiotherapy and chemotherapy is considered necessary. Therefore, the use of radiotherapy alone in early-stage NKTCL is still a controversial issue.5,6 \u0000Read more in PDF.","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 2","pages":"300-301"},"PeriodicalIF":3.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39342495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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