Pub Date : 2024-11-01DOI: 10.21873/anticanres.17321
Jonas M Händelin, Hanna-Riikka Teppo, Kirsi-Maria Haapasaari, Riina K Ollikainen, Janette Kemppainen, Hanne Kuitunen, Outi Kuittinen, Milla E L Kuusisto
Background/aim: Testicular cancers, particularly seminomas and non-seminomas, generally have a favorable prognosis, although a small subset of patients experience mortality. Current knowledge of clinical markers associated with relapse and poor prognosis in seminoma is limited. Chemokines, key proteins in the tumor microenvironment, are underexplored in seminoma prognosis. Additionally, tumor-infiltrating lymphocytes (TILs), which play a critical role in cancer prognosis, require further investigation in the context of seminoma.
Patients and methods: Samples from 25 seminoma patients and 24 control patients who underwent orchiectomy were immunohistochemically (IHC) stained for chemokines CXCR4, CXCR5, and their ligands CXCL12, CXCL13, and the proliferation marker Ki-67. The associations between IHC results and clinical presentations were examined.
Results: Chemokine profiles differed between seminoma and normal testis. The expression of chemokines in TILs in seminoma samples was especially over-expressed. The cytoplasmic expression of CXCL13 in TILs multiplied by the percentage of TILs in each sample, appeared to approach statistical significance concerning the likelihood of relapse.
Conclusion: The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.
{"title":"Chemokine Profile Is Different in Normal Testis Compared to Seminoma - Especially in Tumor Infiltrating Lymphocytes.","authors":"Jonas M Händelin, Hanna-Riikka Teppo, Kirsi-Maria Haapasaari, Riina K Ollikainen, Janette Kemppainen, Hanne Kuitunen, Outi Kuittinen, Milla E L Kuusisto","doi":"10.21873/anticanres.17321","DOIUrl":"https://doi.org/10.21873/anticanres.17321","url":null,"abstract":"<p><strong>Background/aim: </strong>Testicular cancers, particularly seminomas and non-seminomas, generally have a favorable prognosis, although a small subset of patients experience mortality. Current knowledge of clinical markers associated with relapse and poor prognosis in seminoma is limited. Chemokines, key proteins in the tumor microenvironment, are underexplored in seminoma prognosis. Additionally, tumor-infiltrating lymphocytes (TILs), which play a critical role in cancer prognosis, require further investigation in the context of seminoma.</p><p><strong>Patients and methods: </strong>Samples from 25 seminoma patients and 24 control patients who underwent orchiectomy were immunohistochemically (IHC) stained for chemokines CXCR4, CXCR5, and their ligands CXCL12, CXCL13, and the proliferation marker Ki-67. The associations between IHC results and clinical presentations were examined.</p><p><strong>Results: </strong>Chemokine profiles differed between seminoma and normal testis. The expression of chemokines in TILs in seminoma samples was especially over-expressed. The cytoplasmic expression of CXCL13 in TILs multiplied by the percentage of TILs in each sample, appeared to approach statistical significance concerning the likelihood of relapse.</p><p><strong>Conclusion: </strong>The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543266","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 : 2024-11-01DOI: 10.21873/anticanres.17310
Jessica Silva, Tiago Azevedo, Inês Aires, Francisco Peixoto, Maria J Neuparth, Felisbina L Queiroga, Fernanda Seixas, Rita Ferreira, Ana I Faustino-Rocha, José Alberto Duarte, Paula A Oliveira
Background/aim: This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development.
Materials and methods: Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors.
Results: No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group.
Conclusion: WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated.
{"title":"Interplay Between Western Diet and Mammary Cancer: Data from a Chemically-induced Model in Wistar Rats.","authors":"Jessica Silva, Tiago Azevedo, Inês Aires, Francisco Peixoto, Maria J Neuparth, Felisbina L Queiroga, Fernanda Seixas, Rita Ferreira, Ana I Faustino-Rocha, José Alberto Duarte, Paula A Oliveira","doi":"10.21873/anticanres.17310","DOIUrl":"https://doi.org/10.21873/anticanres.17310","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development.</p><p><strong>Materials and methods: </strong>Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors.</p><p><strong>Results: </strong>No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group.</p><p><strong>Conclusion: </strong>WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543310","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}
Background/aim: Pseudoaneurysm formation is a potentially fatal complication after pancreaticoduodenectomy. We developed a packing method in which the gastroduodenal artery stump is packed inside a falciform ligament to reduce the post-pancreatectomy hemorrhage due to pseudoaneurysm formation. This study aimed to evaluate its efficacy.
Patients and methods: This study included 210 patients who underwent pancreaticoduodenectomies between January 2007 and December 2023. The study population was divided into two groups; the packing group (n=110) and the no-packing group (n=100), and the clinical variables were compared between the two groups.
Results: Pseudoaneurysms were observed in six (2.9%) patients, and post-pancreatectomy hemorrhage was observed in four (1.9%) patients. There was no significant difference in pseudoaneurysm formation between the packing and no-packing groups (p=0.477), and the mortality rates for both pseudoaneurysm and post-pancreatectomy hemorrhage were zero. Two patients in the no-packing group were found to have shock, whereas four patients in the packing group (n=4) did not. Additionally, we encountered a 6 cm unruptured pseudoaneurysm following packing.
Conclusion: The packing method did not reduce pseudoaneurysm formation after pancreaticoduodenectomy, but may prevent pseudoaneurysm rupture.
{"title":"Packing of the Gastroduodenal Artery Stump Using Falciform Ligament During Pancreaticoduodenectomy.","authors":"Teruyuki Usuba, Ryota Iwase, Yuichi Nakaseko, Shinji Onda, Yoshihiro Shirai, Masashi Tsunematsu, Masaichi Ogawa, Toru Ikegami","doi":"10.21873/anticanres.17339","DOIUrl":"https://doi.org/10.21873/anticanres.17339","url":null,"abstract":"<p><strong>Background/aim: </strong>Pseudoaneurysm formation is a potentially fatal complication after pancreaticoduodenectomy. We developed a packing method in which the gastroduodenal artery stump is packed inside a falciform ligament to reduce the post-pancreatectomy hemorrhage due to pseudoaneurysm formation. This study aimed to evaluate its efficacy.</p><p><strong>Patients and methods: </strong>This study included 210 patients who underwent pancreaticoduodenectomies between January 2007 and December 2023. The study population was divided into two groups; the packing group (n=110) and the no-packing group (n=100), and the clinical variables were compared between the two groups.</p><p><strong>Results: </strong>Pseudoaneurysms were observed in six (2.9%) patients, and post-pancreatectomy hemorrhage was observed in four (1.9%) patients. There was no significant difference in pseudoaneurysm formation between the packing and no-packing groups (p=0.477), and the mortality rates for both pseudoaneurysm and post-pancreatectomy hemorrhage were zero. Two patients in the no-packing group were found to have shock, whereas four patients in the packing group (n=4) did not. Additionally, we encountered a 6 cm unruptured pseudoaneurysm following packing.</p><p><strong>Conclusion: </strong>The packing method did not reduce pseudoaneurysm formation after pancreaticoduodenectomy, but may prevent pseudoaneurysm rupture.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543271","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}
Background/aim: Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer.
Materials and methods: Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients.
Results: FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases.
Conclusion: This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.
{"title":"Clinical Significance of FAM83G in Breast Cancer: Association With Triple-negative Subtype and Prognosis.","authors":"Takako Ikeda, Chikako Kanno Honda, Sasagu Kurozumi, Takehiko Yokobori, Ayaka Katayama, Kei Masuda, Tetsunari Oyama, Kyoichi Kaira, Jun Horiguchi, Ken Shirabe, Takaaki Fujii","doi":"10.21873/anticanres.17313","DOIUrl":"https://doi.org/10.21873/anticanres.17313","url":null,"abstract":"<p><strong>Background/aim: </strong>Family with sequence similarity 83 member G (FAM83G) plays an important role in cancer aggressiveness and patients' prognosis across various types of cancer. However, the association of FAM83G protein expression in breast cancer with clinicopathologic factors, breast cancer subtypes, and prognosis is not well characterized. This study aimed to elucidate the clinical significance of FAM83G protein expression in breast cancer.</p><p><strong>Materials and methods: </strong>Immunohistochemistry was employed to examine FAM83G protein expression in 75 breast cancer tissues, assessing its potential as a biomarker for breast cancer patients. The Kaplan-Meier plotter was used to estimate the correlation between FAM83G mRNA expression and survival outcomes in TNBC patients.</p><p><strong>Results: </strong>FAM83G protein was predominantly localized in the cytoplasm of breast cancer cells, exhibiting uniform expression throughout tumor tissues. FAM83G expression was significantly higher in cancerous areas compared to non-cancerous areas. High FAM83G expression was more prevalent in triple-negative breast cancer (TNBC) cases than in hormone receptor-positive cases. Although high FAM83G protein expression did not significantly impact prognosis in our cohort, a large-scale database analysis revealed an association between high FAM83G expression and poor prognosis in TNBC cases.</p><p><strong>Conclusion: </strong>This study demonstrates an association between high FAM83G expression in breast cancer tissues and TNBC. FAM83G may serve as a promising biomarker and therapeutic target for breast cancer patients.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543276","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 : 2024-11-01DOI: 10.21873/anticanres.17330
You-Na Sung, Yeseul Kim, Anna Therese Datuin, Inho Jang, Jongmin Sim
Background/aim: Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection.
Patients and methods: The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed.
Results: The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis.
Conclusion: VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.
背景/目的:结直肠癌(CRC)的血管侵犯(VI)是一个独立的预后特征,也是 II 期 CRC 辅助化疗的高风险指标。本研究评估了弹性染色对 VI 检测的影响:采用弹性染色法评估了154例CRC患者的VI。根据苏木精和伊红(H&E)染色,病例被分为三组:无(80 例)、模糊(23 例)和疑似(51 例)。使用弹性染色法对每个病例的两张切片进行 VI 评估,确认其中一张或两张切片上均存在 VI。最后,分析了VI与其他临床病理因素之间的相关性:结果:使用弹性染色法检测 VI 的总检出率为 67/154(51.4%)。在无VI组、模糊组和疑似组中,分别有17/80(21.3%)、3/23(13.0%)和47/51(92.2%)名患者检测到VI。有 28 例患者在弹性染色切片的两个切面中都检测到了 VI,有 38 例患者仅在一个切面中检测到了 VI。VI与神经周围侵犯、M期和同步转移有明显相关性:结论:仅使用 H&E 染色检测 VI 并不可靠,这强调了弹性染色在提高 VI 检测中的重要性。因此,我们建议将弹性染色纳入所有 pT3 和 pT4 CRC 病例的常规病理检查中。
{"title":"Routine Elastic Staining Helps Detection of Vascular Invasion in Colorectal Cancer: A Comprehensive Analysis of T3 or Higher Tumors Without Lymph Node Metastasis.","authors":"You-Na Sung, Yeseul Kim, Anna Therese Datuin, Inho Jang, Jongmin Sim","doi":"10.21873/anticanres.17330","DOIUrl":"https://doi.org/10.21873/anticanres.17330","url":null,"abstract":"<p><strong>Background/aim: </strong>Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection.</p><p><strong>Patients and methods: </strong>The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed.</p><p><strong>Results: </strong>The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis.</p><p><strong>Conclusion: </strong>VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543286","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 : 2024-11-01DOI: 10.21873/anticanres.17295
Sabrina L Zeller, Eris Spirollari, Anisha M Chandy, Simon J Hanft, Chirag D Gandhi, Meena Jhanwar-Uniyal
Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival.
{"title":"Understanding the Genomic Landscape of Glioblastoma: Opportunities for Targeted Therapies.","authors":"Sabrina L Zeller, Eris Spirollari, Anisha M Chandy, Simon J Hanft, Chirag D Gandhi, Meena Jhanwar-Uniyal","doi":"10.21873/anticanres.17295","DOIUrl":"https://doi.org/10.21873/anticanres.17295","url":null,"abstract":"<p><p>Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543289","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 : 2024-11-01DOI: 10.21873/anticanres.17315
Hye Min Lee, Hee Jin Cho, Yul Min Lee, Hyun Jung Kim, Kyun Heo
Background/aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer.
Materials and methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes.
Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction.
Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.
{"title":"Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction.","authors":"Hye Min Lee, Hee Jin Cho, Yul Min Lee, Hyun Jung Kim, Kyun Heo","doi":"10.21873/anticanres.17315","DOIUrl":"https://doi.org/10.21873/anticanres.17315","url":null,"abstract":"<p><strong>Background/aim: </strong>Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer.</p><p><strong>Materials and methods: </strong>The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes.</p><p><strong>Results: </strong>Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction.</p><p><strong>Conclusion: </strong>Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543295","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}
Background/aim: The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line.
Materials and methods: We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression.
Results: We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5.
Conclusion: Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.
{"title":"Differential Effects of Punicic Acid on Cytotoxicity and Peroxiredoxin Expression in MCF-7 Breast Cancer and MCF-10A Normal Cells.","authors":"Braden Quitmeyer, Chiemelie Emelife, Hannah Klausner, Oluwafemi Gbayisomore, Shelley Phelan","doi":"10.21873/anticanres.17301","DOIUrl":"10.21873/anticanres.17301","url":null,"abstract":"<p><strong>Background/aim: </strong>The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line.</p><p><strong>Materials and methods: </strong>We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression.</p><p><strong>Results: </strong>We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5.</p><p><strong>Conclusion: </strong>Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543292","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}
Background/aim: The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC.
Materials and methods: We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC.
Results: In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC.
Conclusion: Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.
{"title":"Lymphocyte Antigen 6 Family Member D (LY6D) Affects Stem Cell Phenotype and Progression of Pancreatic Adenocarcinoma.","authors":"Shumpei Okimura, Naohiro Nishida, Hidekazu Takahashi, Yuhki Yokoyama, Hiroyuki Yamamoto, Atsushi Hamabe, Takayuki Ogino, Norikatsu Miyoshi, Hidenori Takahashi, Mamoru Uemura, Shogo Kobayashi, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto","doi":"10.21873/anticanres.17300","DOIUrl":"10.21873/anticanres.17300","url":null,"abstract":"<p><strong>Background/aim: </strong>The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC.</p><p><strong>Materials and methods: </strong>We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC.</p><p><strong>Results: </strong>In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC.</p><p><strong>Conclusion: </strong>Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543315","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 : 2024-11-01DOI: 10.21873/anticanres.17296
Sara Cocchi, Joanna Lopacinska-Jørgensen, Estrid V Høgdall
Background/aim: Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy.
Materials and methods: We conducted a three-step search process on PubMed to systematically review English-language articles published between 2020 and 2024. From the 123 articles retrieved, we included 11 articles that investigated transcriptomic signatures by RNA sequencing in tissues from chemo-sensitive and -resistant HGSOC patients.
Results: We report the clinicopathological data of 727 patients in the experimental cohorts, transcriptomic signatures, and technical aspects. Finally, the review lists 15 publicly available datasets used in the included studies. Furthermore, we investigated the overlap of 167 differentially expressed genes retrieved across the various articles.
Conclusion: We believe this review might offer valuable insights for further studies focusing on predicting platinum resistance and personalized treatments. In addition to discussing the latest findings and potential candidates, we highlight the challenges of validating biomarkers across studies and publicly available datasets. Transcriptomic signatures represent a potential tool for patient stratification, prognosis, and the potential adoption of long-term therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPis).
{"title":"Potential Transcriptomic Biomarkers for Predicting Platinum-based Chemotherapy Resistance in Patients With High-grade Serous Ovarian Cancer.","authors":"Sara Cocchi, Joanna Lopacinska-Jørgensen, Estrid V Høgdall","doi":"10.21873/anticanres.17296","DOIUrl":"https://doi.org/10.21873/anticanres.17296","url":null,"abstract":"<p><strong>Background/aim: </strong>Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy.</p><p><strong>Materials and methods: </strong>We conducted a three-step search process on PubMed to systematically review English-language articles published between 2020 and 2024. From the 123 articles retrieved, we included 11 articles that investigated transcriptomic signatures by RNA sequencing in tissues from chemo-sensitive and -resistant HGSOC patients.</p><p><strong>Results: </strong>We report the clinicopathological data of 727 patients in the experimental cohorts, transcriptomic signatures, and technical aspects. Finally, the review lists 15 publicly available datasets used in the included studies. Furthermore, we investigated the overlap of 167 differentially expressed genes retrieved across the various articles.</p><p><strong>Conclusion: </strong>We believe this review might offer valuable insights for further studies focusing on predicting platinum resistance and personalized treatments. In addition to discussing the latest findings and potential candidates, we highlight the challenges of validating biomarkers across studies and publicly available datasets. Transcriptomic signatures represent a potential tool for patient stratification, prognosis, and the potential adoption of long-term therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPis).</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543273","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}