bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whose mitochondria are more stable, male or female ones? Response of neurosteroid status of mitochondria of cerebral cortex cells to melanoma development in presense of chronic pain.
Authors: Neskubina Irina V. , Frantsiyants Elena M. , Kaplieva Irina V. , Shikhlyarova Alla I. , Surikova Ekaterina I. , Cheryarina Natalia D. , Bandovkina Valeria A. , Pogorelova Yulia A. , Kuchkina Ludmila P. , Snezhko Aleksandr V. , Rozenko Dmitry A. , Ausheva Tatiana V. , Kit Oleg I. 
Published: June 2022

e21559 Background: Gender differences in brain physiology and gender differences in pathology are usually recognized, but often are disregarded in clinical and experimental studies, resulting in numerous inaccuracies in data interpretation. The purpose of this study was to analyze levels of neurosteroid hormones in mitochondria of the cerebral cortex cells in C57BL/6 mice with subcutaneous B16/F10 melanoma growing in presence of chronic neurogenic pain (CNP). Methods: The study included male and female C57BL/6 mice (n = 336) aged 8 weeks initially weighing 21-22 g. Experimental groups were: intact animals; controls with a CNP model created by bilateral sciatic nerve ligation; comparison group 3 weeks after subcutaneous inoculation of 0.5 ml suspension of B16/F10 melanoma cells diluted 1:10; main group 3 weeks after subcutaneous melanoma growth in presence of CNP (CNP+B16/F10). Levels of estradiol (pg/g protein), estrone (pg/g protein) (DBC, Canada); progesterone (ng/g protein), total and free testosterone (pg/g protein) (XEMA, Russia) were measured in mitochondrial samples by ELISA (Tecan Infinite F50 analyzer, Austria). Results: Levels of estradiol in intact females were 3.1 times higher than in males, while estrone, progesterone, total and free testosterone were lower by 6.4, 2.7, 2.0 and 2.5 times, respectively. Only in females with CNP estradiol decreased by 3.4 times, compared to intact values, and estrone increased by 1.7 times (p<0.05), testosterone by 3.9 times. Estradiol in animals with B16/F10 decreased compared with intact values by 3.1 times in females and by 1.5 times in males (p<0.05). Females with B16/F10 showed the highest levels of progesterone exceeding intact values by 3.1 times. In the group with CNP+B16/F10, females showed lower levels of estradiol and estrone (by 1.4 times, p<0.05) and free testosterone (by 1.6 times, p<0.05), compared to the levels in CNP; on the opposite, males had 1.5 times (p<0.05) higher estrone and 2.9 times lower progesterone. Conclusions: Low levels of estradiol involved in the protective mechanism of neurosteroids were the dominant factor in mitochondria of cerebral cortex cells in females with CNP and malignant neoplasms. Males did not demonstrate such dominant factor. In animals with CNP+B16/F10, the response nature of cerebral cortex mitochondria changed: all defense mechanisms in the brain of females were suppressed by the 3rd week of tumor development in presence of pain. In males, mitochondria of cerebral cortex cells were more resistant to the influence of two pathologies, and only few changes in the neurosteroid status were recorded.
Dietary fish oil augments the tumor immune microenvironment in anti-PD-1 treated melanoma.
Authors: Chacon Alexander C , Qin Shuyang Sue , Melucci Alexa , Jackson Katherine M. , Burchard Paul R. , Dave Yatee A. , Jewell Rachel , Belt Brian A. , Tabayoyong William , Prieto Peter A. 
Published: June 2022

e21564 Background: Less than half of metastatic melanoma patients experience objective responses to first line anti-PD-1 immune checkpoint inhibition (αPD-1 ICI). Omega-3 fatty acids in dietary fish oil (FO) shift myeloid and T-cell populations to anti-inflammatory, pro-resolution phenotypes in immunity and cancer. We investigated whether dietary FO supplementation could augment tumor microenvironment (TME) immune profiles and improve ICI response in melanoma. Methods: C57-BL6/J mice were injected with YUMM 1.7 melanoma in the flank. Mice were fed control chow (CTL) or omega-3 rich (FO) chow (10% w/w, 30%kcal/kcal) starting 7 days post tumor implantation. Intraperitoneal αPD1 or IgG2a vehicle were injected q3-4 days starting day 12. To assess the temporal flux of TME immune populations, tumors from mice in analogous experiments were assessed for growth, harvested on day 12, day 22, or day 32, and characterized via flow cytometry. Results: In multiple models, FO decreased YUMM tumor growth vs. CTL by day 32 (> 21% for all models). FO halved tumor associated macrophage content, including M2 macrophages (Arg1+, CD206+, CD68+, F480+), at day 12. Conversely, FO increased M2 macrophages at day 22, leveling even with CTL at day 32. At all three timepoints, FO increased TME monocytes (Ly6C+, Ly6G-). In the T cell compartment, FO decreased TME CD4 and CD8 T cell content (including PD1+ CD4 and PD1+ CD8) at day 12, an effect which was reversed by day 22 (increased CD4 and CD8s vs CTL). FO increased PD-L1+ CD4 T cells and CD8+ T cells, including PD1+ CD8 T cells, on day 32. When fish oil diets were started on day 12 (concurrent with immunotherapy), FO decreased tumor volume, increased monocytes (and PD-L1+ monocytes), and increased CD4 and PD1+ CD8 T cells by day 32, all less significantly than when starting diets 5 days prior to initiation of immunotherapy. All results significant (p < 0.05) by 2-way ANOVA or t-test unless specified. Food eaten, water imbibed, and weight change did not vary between groups. Conclusions: Fish oil impairs in vivo murine melanoma tumor growth with and without αPD-1 ICI. Fish oil modulated myeloid and T cell lineages via delaying M2 macrophage and CD4 / CD8 T-cell appearance in the tumor microenvironment, with concomitant increases in monocytes and key T cell effectors involved in αPD-1 ICI responsiveness by the time decrements in tumor growth were noted. Dietary fish oil may benefit patients with advanced melanoma treated with αPD-1 immunotherapy; further study in humans is warranted.
Survey of Uruguayan women on knowledge related to the prevention of breast cancer.
Authors: Camejo Natalia , Castillo Cecilia , Amarillo Dahiana , Bernate Moira , Burguez Florencia , Darino Eliana , Deleon Adrian , Milwa Tatiana , Barcia Maria , Krygier Gabriel David 
Published: June 2022

e22504 Background: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Methods: To assess the knowledge of Uruguayan women about breast cancer screening for the early detection of BC. Material and Methods: This is a descriptive and observational study. A survey was applied to womwn, it was disseminated through social networks. Informed consent was requested at the beginning of the survey as an exclusive requirement to be able to carry it out. In the statistical analysis, the anonymity of the patients was maintained and the approval of the Ethics Committee of the Hospital de Clínicas was obtained. Results: 1859 women participated. 75.1% (1396) of those surveyed recognize BC as the one with the highest mortality in women. 52% (967) believe that 3 out of 10 women are at risk of developing BC, and 18.4% (342) do not know its prevalence. 60.2% (1119) recognize mammography as a test that has managed to reduce mortality from BC. 64.2% (1193) believe that it is done after 40 years of age. Regarding the frequency, 60.5% (1125) consider that it is carried out annually. The most considered risk factors for developing BC were smoking (60.9%, 1132), obesity (57%, 1.060) and sedentary lifestyle (56.8%, 1056). Conclusions: Our results show that the respondents are adequately informed about the importance of CM and the performance of screening mammography.
Deciphering possible mechanisms of action in pathophysiology of osteosarcoma: PI3K-Akt/MAPK pathways contribute to tumorigenesis versus FoxO/mTOR/HIF-1 pathways involved in metastasis.
Authors: Zou Changye , Zhao Zhiqiang , Xu Mingxian , Guo Weitang , Huang Jintao , Zhang Xin , You Dong , Shen Jingnan 
Published: June 2022

e23515 Background: Osteosarcoma is a kind of primary bone malignancies with high invasiveness and poor prognosis. However, effective therapy for osteosarcoma is still lacking. In fact, the advancement of clinical practice and innovative therapy was hindered by the limited understanding of the genetic characteristics and the mechanism of metastasis. Exploration of the mutational and evolutionary features of osteosarcoma is warranted. Methods: A total of 24 samples of matched primary and metastatic lesions were collected from 12 osteosarcoma patients. Targeted sequencing including 672 cancer-related genes was conducted in 9 patients while whole exome sequencing was performed in 3 patients. Results: High-frequency mutation genes were TP53 (42%), FLCN (33%), GID4 (33%), ATRX (25%), CCND3 (25%) in primary osteosarcoma, comparing to FLCN (42%), GID4 (42%), CCNE1 (25%), MYO15A (25%), ATRX (25%) in metastatic lesion. The PI3K-Akt and MAPK signaling pathway was significantly enriched in both primary (PI3K, p < 0.001; MAPK, p < 0.001) and metastatic lesions. (PI3K, p < 0.001; MAPK, p < 0.001), Additionally, chromosome region 17p11.2, including the driver genes NCOR1, MAP2K4, ALOX12B, AURKB, CDK12, was significantly amplified in primary (G-score = 1.9, q-value = 0.06) and metastatic lesions (G-score = 3.2, q-value < 0.001). These data suggested that changes of PI3K and MAPK pathways and amplification of region 17p11.2 may contribute to initial osteosarcoma tumorigenesis and possibly early metastasis. In contrast, the FoxO, mTOR and HIF-1 signaling pathway were only enriched in metastatic lesions (FOXO, p < 0.001; mTOR, p < 0.05; HIF-1, p < 0.001), implying that these pathways may be critical for osteosarcoma metastatic occurrence. Finally, clonality analysis showed that cellular clonal prevalence (CCF) of subclones including diver genes of ATRX, MYO15A and MYB, were increased ( ATRX: P, CCF = 0.59, M, CCF = 0.74; MYO15A: P, CCF = 0.43, M, CCF = 0.52; MYB: P, CCF = 0.11, M, CCF = 0.52) in metastatic lesions, which further confirmed that alterations of ATRX and MYO15A were considerably vital for osteosarcoma. Conclusions: The abnormal changes of PI3K-Akt and MAPK signaling pathway as well as the amplification of 17p11.2 chromosome region may contribute to osteosarcoma tumorigenesis and possibly early metastasis; whereas pathways of FoxO, mTOR, HIF-1 and driver genes including ATRX, MYO15A and MYB, may play a key role in the metastasis of osteosarcoma.
Tumor thrombosis in extremity soft tissue sarcomas.
Authors: Katelnitskaya Oksana V. , Nepomnyashchaya Evgeniya M. , Ausheva Tatiana V. , Barashev Artem A. , Vashchenko Larisa N. , Chernogorov Pavel V. , Kit Oleg I. 
Published: June 2022

e23551 Background: Malignant tumors of bones and soft tissues often reach large sizes, compress and invade the major vessels, leading to the development of venous thrombosis. Venous thrombosis is difficult to distinguish from tumor thrombosis in the preoperative period. However, the management differs. Both conditions require anticoagulant therapy, but tumor thrombosis requires expanding intervention with the thrombus removal and major venous resection. The major vessel involvement complicates surgery. It is much more difficult to achieve negative resection margins. The risk of damage to the main vessels during tumor mobilization increases and, as a result, the risk of hemorrhagic complications increases as well. An interdisciplinary approach reduces the risk of surgical complications and helps achieve radical tumor resection. Our purpose was to analyze the rates of tumor thrombosis in malignant tumors of bones and soft tissues and evaluate the results of surgical treatment. Methods: 115 patients (mean age 46 years) with malignant tumors of bones and soft tissues received surgical treatment in 2020-2021. The most common histological subtypes were synovial sarcoma (25.3%), pleomorphic sarcoma (18.2%), and liposarcoma (15.6%). Venous thrombosis of the lower extremity veins was diagnosed at the stage of preoperative preparation in 17 patients (14.8%), the femoral segment was more often affected (70.6%). All patients received anticoagulant therapy. The tumor genesis of a thrombus was confirmed intraoperatively in 7 patients. Thus, the incidence of tumor thrombosis in malignant tumors of bones and soft tissues was 6%. All patients underwent tumor removal, thrombectomy, and the femoral or iliac venous segment resection. Results: The following complications were observed in the postoperative period: seroma - 5 cases (29.4%), lymphorrhea - 12 (70.5%), swelling of the lower limb - 12 cases (70.5%). Conclusions: Tumor thrombosis in malignant tumors of bones and soft tissues of the lower extremities is not a rare complication, it requires timely diagnosis and an expanded intervention to achieve negative resection margins and reduce the risk of embolism.
Differential outcome of females with uterine versus extra-uterine leiomyosarcomas, a retrospective analysis.
Authors: Hana Caroline , Akinbobuyi Olufunke , Wadhawan Ashna , Samuels Shenae , Hussein Atif Mahmoud 
Published: June 2022

e23557 Background: Leiomyosarcomas, are aggressive sarcomas with survival rates among the lowest of all soft tissue sarcomas. Patients with uterine leiomyosarcoma (ULMS) have worse overall survival (OS) than those with extra-uterine leiomyosarcoma (EULMS). The effect of several clinical factors on OS have been investigated, including age, tumor size, grade, stage, and use of chemotherapy. Looking at the epigenetics of the 2 diseases, differentially methylated regions (DMRs) were statistically significant between the 2 groups. Methods: The 2004-2016 National Cancer Database was queried for females with ULMS and EULMS. We investigated several factors as predictors of binary survival status (alive or dead): patient’s age, race, year at diagnosis, tumor grade, size and stage, receipt of surgical treatment, chemotherapy, palliative care, surgical margins and time to treatment in days. Univariate and backward stepwise multivariate logistic regression models were used to determine prognostic factors associated with survival in each group. Kaplan-Meier (KM) method with log-rank test was used to compare OS rates between the 2 groups. All analyses were conducted using Stata/SE 15.1. Results: The total number of subjects was 16883. The median OS was 36.7 months in ULMS vs 57.2 in EULMS (P < 0.001). Older age was associated with a lower likelihood of survival in both groups (OR = 0.95, P = 0.018 in ULMS; OR = 0.97, P < 0.001 in EULMS). Lymphovascular invasion and receipt of palliative care were associated with a relatively large decrease in survival in ULMS only (OR = 0.25, P < 0.001; OR = 0.13, P = 0.015 respectively). In the EULMS group, increased likelihood of survival was associated with later years of diagnosis (OR = 1.27; P < 0.001). Larger tumor size (OR = 0.39; P = 0.001), stages II-IV or unstageable disease (OR = 0.56; P < 0.001), positive surgical margins or margins that were unevaluable (OR = 0.87; P = 0.009) and receipt of systemic therapy (OR = 0.85; P = 0.016) were associated with a lower likelihood of survival. Conclusions: Our study reiterated that females with ULMS had worse OS than those with EULMS. this difference can be attributed to certain clinical risk factors, however, it may also be secondary to genetic and epigenetic factors. Surprisingly, the use of palliative care in this study was associated with poorer OS in the EULMS group. Further studies are needed to investigate the genetic map of these diseases and highlight certain potentially targetable prognostic and predictive factors. Study limitations: Our study did not stratify ULMS and EULMS according to the stage to examine if the aforementioned factors would still be relevant in the limited versus metastatic setting.
Evaluating cancer awareness months and cancer screening tests through internet search big data.
Authors: Tawfik Bernard 
Published: June 2022

e24038 Background: Cancer Awareness Months (CAMs) aim to increase public recognition of specific cancers through education and screening promotion, but their effectiveness is uncertain. This study was designed to characterize the relationship between internet search interest (ISI) of breast, colon, lung, and prostate cancers and related screening test terms with their respective CAMs with the goal of better understanding CAM effectiveness across time and geographic scale. Methods: ISI was collected from sampled Google Search data from Google Trends on a national, state, and metropolitan level between 2004 and 2021. The ISI for cancer and cancer screening terms for each respective CAM was compared to ISI for nonadjacent months and across regionality. Results: Breast CAM was associated with increased ISI for both cancer (p > 0.001) and cancer screening (p > 0.001) terms. Colon CAM was associated with higher cancer term ISI (p = 0.004), but had mixed effects on screening ISI across terms. Lung CAM was not associated with a change in cancer term ISI (p = 0.573) and had mixed effects across screening terms. Prostate CAM was not linked to ISI changes for any associated terms. Regional variation in ISI was found in all cases. Conclusions: Given the high accessibility and scalability of Google Trends, this tool can be used to practically evaluate and guide the strategies of CAM campaigns across cancer type and geographic scale. Future directions include broadening the geographic scope and comparatively assessing specific CAM campaign strategies.
“The Oizys Study”: Prevalence and impact of scan-related anxiety on QoL among Greek cancer patients and their caregivers.
Authors: Koinis Filippos , Leontopoulou Vasiliki , Chantzara Evangelia , Kotsakis Athanasios 
Published: June 2022

e24118 Background: Diagnostic imaging may be a major source of distress in patients with advanced cancer, a condition known as “scanxiety”. Scanxiety represents a complex array of negative and stressful emotions linked with cancer scans, and the uncertainties and fears that may accompany them. We aimed to evaluate the prevalence and characterize risk factors for scanxiety among cancer patients and their caregivers and evaluate the impact of scanxiety on quality of life (QoL), during the COVID-era. Methods: We conducted a cross-sectional survey study of metastatic cancer patients treated at the University Hospital of Larisa and their caregivers. Eligible patients met the following inclusion criteria: age > 18 years old, ability to speak and write fluently in Greek, having had at least one imaging study during the period of the study ( seven days before the survey), approval of the patient’s oncologist to approach the patient. Patients/caregivers with pre-existing (prior to cancer diagnosis anxiety disorder) were excluded from the study. After completion of the informed consent process, patients/caregivers completed all survey items. We used a modified version of the Greek version of the Impact of Event Scale-Revised (IES-R-Gr) to specifically assess distress associated with scans, and QoL was measured using the EORTC QLQ-C30 questionnaire. Results: 218 patients with metastatic cancer and their caregivers were included in the study. Patient's mean age was 66 years (range 35-88). The majority were men (61%) and were diagnosed with Non-Small-Cell Lung Cancer. 71% had an IES-R-Gr score that was suggestive of scanxiety. Their symptoms were more severe symptoms while waiting for the results. Patients with a recent diagnosis (< 6 months) had higher levels. Interestingly, 16% of the patients had postponed a check-up due to scanxiety, while 77% reported that stress does not decrease over time. The majority of caregivers (81%) reported scanxiety, without a strong correlation with the score of the respective patients. Unlike patients, the majority of caregivers reported an increase in stress during the COVID-19 period. The presence of scanxiety was associated with decreased QoL in patients (p = 0.004). Conclusions: Scanxiety is a common problem among patients with metastatic cancer and is associated with impaired QoL. To our knowledge this is the first study implying that caregivers also experience scanxiety and may be a persistent problem.
A first-in-human, phase I, open-label study of a novel cancer vaccine labvax 3(22)-23 and adjuvant GM-CSF in patients with advanced stage adenocarcinomas.
Authors: Ma Weijie , Chen Shuai , Ogihara Nancy L. , Huynh Jasmine , Yen Ariel , Kelly Karen , Lara Primo "Lucky" N. , Radosevich James A. , Babich Michael , Li Tianhong 
Published: June 2022

TPS2700 Background: Adenocarcinoma is the most common histologic type of solid tumors and can arise from almost anywhere in the body. Labyrinthin is a novel tumor-specific protein expressed on the cell surface of the majority of adenocarcinomas of various cancer types. Several therapeutic strategies targeting labyrinthin are under development. We hypothesize that vaccination against labyrinthin can elicit strong immune responses against the labyrinthin-positive adenocarcinomas in cancer patients. LabVax 3(22)-23 is a novel anti-tumor vaccine that contains 4 synthetic labyrinthin-based peptides designed to elicit both B-cell and T-cell responses. Sargramostim, a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF), is given as an immunostimulator with LabVax 3(22)-23 to boost the antitumor immune response. Preclinical studies showed that LabVax 3(22)-23 significantly inhibited tumor growth that was augmented by GM-CSF without any significant toxicity in C57/BL6 transgenic mice expressing human PD-1/PD-L1 implanted with the murine colon adenocarcinoma cell line MC-38-huPD-L1. This single institution, first-in-human, phase I trial (UCDCC#296) evaluates LabVax 3(22)-23 and adjuvant sargramostim in patients with labyrinthin-positive metastatic or recurrent adenocarcinoma of any primary tumor site after all standard-of-care therapies. Methods: The primary objective is to assess the toxicity of LabVax 3(22)-23 and adjuvant sargramostim according to NCI CTCAE V5.0. The primary endpoint is dose limiting toxicity (DLT), which is defined as grade ≥ 2 allergic and autoimmune reaction, grade ≥ 3 injection site reaction, any grade 3 toxicities lasting >1 week, or any grade ≥ 4 toxicities. With a sample size of 10 patients, there is 89-97% of chance to observe ≥1 DLT if the true event rate is 20-30%. A secondary endpoint is the preliminary assessment of tumor response rate by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Exploratory objectives measure the effect of LabVax 3(22)-23 on various immune responses (cytokines, anti-labyrinthin antibody production) and the correlation between the level of labyrinthin expression and the efficacy of LabVax 3(22)-23. Eligible patients are required to have labyrinthin expression on their tumor cells by immunohistochemistry and adequate organ function. Patients receive sargramostim subcutaneously and LabVax 3(22)-23 intradermally on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year. Two patients are enrolled at the time of submission. Clinical trial information: NCT05101356.