Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

Catharina Johanna Alberts, Paul Bloem, Silvia deSanjosé et al.

The main infections that cause cancer in the European Union (EU) are Helicobacter pylori (H. pylori), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Altogether, in 2022, these infections accounted for ~ 5% of all cancers in the EU, mainly of the stomach, cervix uteri and liver. The largest burden of infection‐caused cancers was found in the south of the EU and near the eastern border. Substantial progress in the efficacy of interventions against these infections has been made since the release of the 4th edition of the European Code Against Cancer in 2015. Cancers due to infections can increasingly be prevented by prophylactic vaccines (HPV and HBV) and/or prompt diagnosis and treatment that can either cure (HCV and H. pylori) or slow down the infection (HBV and HIV), thus substantially reducing disease risk. Tools to tackle carcinogenic infections are also increasingly accessible and affordable in the EU, but their implementation is slow. Public awareness, political will and cost‐effective protocols are necessary to establish large programmes of vaccination or testing and treatment. Progress monitoring, as well as avoiding disinformation and stigma, is crucial to ensure that advances in medical progress are fully leveraged. The recently published 5th edition of the European Code Against Cancer therefore recommends: (1) vaccinate girls and boys against HBV and HPV at the age recommended in your country; (2) take part in testing and treatment for HBV and HCV, HIV and H. pylori, as recommended in your country.

Yong Shen, Yong Xia, Yinyin Chang et al.

Abstract Cancer is a critical global health issue, especially in low- and middle-income countries (LMICs). In this study, we integrated four additional cohorts to assess the performance and robustness of an AI-empowered blood-based test (named OncoSeek) for multi-cancer early detection (MCED). It included a case-control cohort of symptomatic cancer patients, a prospective blinded study, and two retrospective cohorts conducted on two distinct platforms. Combining these with previously published one training and two validation cohorts, we evaluated OncoSeek’s performance in 15,122 participants (3029 cancer patients and 12,093 non-cancer individuals) from seven centres in three countries, using four platforms and two sample types. OncoSeek showed adequate performance for MCED with an area under the curve (AUC) of 0.829, 58.4% sensitivity, 92.0% specificity, and overall accuracy of 70.6% in tissue of origin (TOO) prediction for the true positives. The test could detect 14 common cancer types, accounting for 72% of global cancer deaths, with sensitivities ranging from 38.9 to 83.3%. Additionally, the symptomatic cohort exhibited a high sensitivity of 73.1% at 90.6% specificity, indicating OncoSeek’s potential for cancer early diagnosis. These findings underscore OncoSeek’s consistent performances across diverse populations, platforms, and sample types, offering affordable and accessible multi-cancer early detection, especially for LMICs.

Stephanie Franco, Lucy A. Godley

Brendan Moloney, Xin Li, Michael Hirano et al.

Quantitative dynamic contrast-enhanced (DCE) MRI as a promising method for the prediction of breast cancer response to neoadjuvant chemotherapy (NAC) has been demonstrated mostly in single-center and single-vendor platform studies. This preliminary study reports the initial experience in implementing quantitative breast DCE-MRI in multi-center (MC) and multi-vendor platform (MP) settings to predict NAC response. MRI data, including B1 mapping, variable flip angle (VFA) measurements of native tissue R1 (R1,0), and DCE-MRI, were acquired during NAC at three sites using 3T systems with Siemens, Philips, and GE platforms, respectively. High spatiotemporal resolution DCE-MRI was performed using similar vendor product sequences with k-space undersampling during acquisition and view sharing during reconstruction. A breast phantom was used for quality assurance/quality control (QA/QC) across sites. The Tofts model (TM) and shutter-speed model (SSM) were used for pharmacokinetic (PK) analysis of the DCE data. Additionally, tumor region of interest (ROI)- vs. voxel-based analyses in combination with the use of VFA-measured R1,0vs. fixed, literature-reported R1,0 were investigated to determine the optimal analysis approach. Results from 15 patients who completed the study are reported. Voxel-based PK analysis using fixed R1,0 was deemed the optimal approach, which allowed the inclusion of data from one vendor platform where VFA measurements produced ≥100% overestimation of R1,0. The semi-quantitative signal enhancement ratio (SER) and quantitative PK parameters outperformed the tumor longest diameter (LD) in the prediction of pathologic complete response (pCR) vs. non-pCR after the first NAC cycle, whereas Ktrans consistently provided more accurate predictions than both SER and LD after the first NAC cycle and at the NAC midpoint. Both TM and SSM Ktrans and kep were excellent predictors of response at the NAC midpoint with ROC AUC >0.90, while the SSM parameters (AUC ≥0.80) performed better than their TM counterparts (AUC <0.80) after the first NAC cycle. The initial experience of this ongoing study indicates the importance of QA/QC using a phantom and suggests that deploying voxel-based PK analysis using a fixed R1,0 may mitigate random errors from R1,0 measurements across platforms and potentially eliminate the need for B1 and VFA acquisitions in MC and MP trials.

Chad Brenner, Chad Brenner, Carolyn Y. Fang

Haia Khoury, Stefano Cairo, Mara Gilardi et al.

Genomic DNA editing is a continuous process that occurs during the entire cell life span. The type and frequency of these modifications can be related to the physiological or pathological activity of intrinsic mechanisms such as DNA surveillance and repair or to extrinsic events that may induce an alteration of DNA sequence by exposure to agents that directly or indirectly induce accumulations of DNA alterations. In the past few years, large-scale analyses have revealed mutational signatures across human cancer types. These signatures can be used as markers of defective internal processes, such as DNA repair deficiency, or external exposures, such as carcinogens, like tobacco, or genotoxic therapies such as radiation and chemotherapy. Our TumorGraft platform, a collection of 1500 patient-derived xenograft generated from more than 50 different types of cancer, is one of the most comprehensive preclinical oncology platforms worldwide, and aims to recapitulate the variety of the patient population and tumor biology complexity. This platform is currently used to evaluate the efficacy of new drugs, and all our models are very well characterized at the molecular level, including whole transcriptome, proteomics and phospho-proteomics, quantification, and genomic variation calls. This allows accurate selection of models with the molecular characteristics of the target patient population, as well as to identify biomarkers predictive of treatment efficacy. This could eventually lead to the development of companion biomarkers in the clinical setting to improve the identification of patients that will benefit from the treatment and those that should be spared. To maximize the chances of identifying relevant molecular traits associated with tumor response, we have been utilizing the Pharmaco-Pheno-Multiomic (PPMO) integration workflow, a machine learning approach which combines phenotypic and therapeutic response profiles with multiple omics datatypes to generate complex biomarker profiles. To provide additional insights on the molecular characteristics of our tumors, we decided to perform the mutational signatures profiling of our models by using whole exome sequencing data. The results obtained were crossed with patient’s clinical history and showed good correlation between the mutational signatures identified and the treatments received by the patient, in particular for exposure to platinum salts. The addition of PDXs mutational signatures strongly improves our knowledge on these models and confers an important parameter for model selection. Moreover, the integration of mutational signature profiles in the PPMO workflow would make a significant contribution for companion biomarkers identification. Citation Format: Haia Khoury, Stefano Cairo, Mara Gilardi, Michael Ritchie, Gilad Silberberg. Mutational signatures in PDXs for improved understanding of drug response and companion biomarkers identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7115.

Mohammed Abusuliman, A. M. Mohamed, Anas Mahmoud et al.

Malignant pericardial effusion (MPE) is a slowly progressive and potentially clinically silent condition. Pericardial effusion can arise in oncology patients due to several factors, including disease spreading directly or metastatically, anticancer therapy side effects, or both. Solid and hematological malignancy metastasis more frequently involves the pericardium than primary tumors, with lung cancer being the most common metastatic tumor to involve the pericardium. While 5%-20% of all patients with metastatic neoplasms have pericardial involvement, MPE rarely appears with hemodynamic instability. Occasionally, MPE constitutes the initial manifestation of an underlying malignancy. Diagnosis and treatment require a multidisciplinary approach and a high degree of clinical suspicion. We present a case of a 59-year-old female with a history of peritoneal carcinoma who presented with persistent dyspnea on exertion following an episode of pneumonia that was treated with antibiotics. Physical examination and bedside point-of-care ultrasound (POCUS) revealed fluid in the pericardial sac. The cytological examination of the fluid revealed it to be of malignant origin, resulting from metastasis from gynecologic adenocarcinoma. Pericardiocentesis was done, and symptoms improved after fluid drainage.

Jiu Chen, Tianxiao Fu, Li Liu et al.

IntroductionAcupuncture has been shown to be effective in restoring gastrointestinal function in tumor patients receiving the enhanced recovery after surgery (ERAS) protocol. The present systematic review and meta-analysis aimed to evaluate the rationality and efficacy of integrating acupuncture in the ERAS strategy to recuperate gastrointestinal function.MethodsWe searched eleven databases for relevant randomized clinical trials (RCTs) of acupuncture for the treatment of gastrointestinal dysfunction in tumor patients treated with the ERAS protocol. The quality of each article was assessed using the Cochrane Collaboration risk of bias criteria and the modified Jadad Scale. As individual symptoms, the primary outcomes were time to postoperative oral food intake, time to first flatus, time to first distension and peristaltic sound recovery time (PSRT). Pain control, adverse events, and acupoint names reported in the included studies were also investigated.ResultsOf the 211 reviewed abstracts, 9 studies (702 patients) met eligibility criteria and were included in the present systematic review and meta‑analysis. Compared to control groups, acupuncture groups showed a significant reduction in time to postoperative oral food intake [standardized mean difference (SMD) = -0.77, 95% confidence interval (CI) -1.18 to -0.35], time to first flatus (SMD=-0.81, 95% CI -1.13 to -0.48), time to first defecation (SMD=-0.91, 95% CI -1.41 to -0.41, PSRT (SMD=-0.92, 95% CI -1.93 to 0.08), and pain intensity (SMD=-0.60, 95% CI -0.83 to -0.37).The Zusanli (ST36) and Shangjuxu (ST37) acupoints were used in eight of the nine included studies. Adverse events related to acupuncture were observed in two studies, and only one case of bruising was reported. DiscussionThe present systematic review and meta‑analysis suggested that acupuncture significantly improves recovery of gastrointestinal function and pain control in tumor patients receiving the ERAS protocol compared to the control group. Moreover, ST36 and ST37 were the most frequently used acupoints. Although the safety of acupuncture was poorly described in the included studies, the available data suggested that acupuncture is a safe treatment with only mild side effects. These findings provide evidence-based recommendations for the inclusion of acupuncture in the ERAS protocol for tumor patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023430211.

Shanshan Chen, Shanshan Chen, Anghui Peng et al.

Immunotherapy has greatly enhanced the effectiveness of cancer treatments, but the efficacy of many current immunotherapies is still limited by the tumor-suppressive immune microenvironment. Multiple studies have shown that activating the stimulation of IFN genes (STING) pathway and inducing innate immunity can significantly impact the tumor immune microenvironment and improve antitumor therapy. While natural or synthetic STING agonists have been identified or developed for preclinical and clinical use, small molecule agonists have limited utility due to degradation and lack of targeting. As such, the delivery and release of STING agonists into tumor tissue is a major challenge that must be addressed in order to further advance the use of STING agonists. To address this challenge, various nanomedicines have been developed. In this paper, we concisely review the antitumor immunotherapeutic mechanisms of STING agonists, highlighting the latest developments in STING agonists and the current progress of nanomedicines for activating STING. We classify the different nanomedicines according to the STING agonists they utilize in order to facilitate understanding of recent advances in this field. Finally, we also discuss the prospects and challenges of this field.

Hyun Sik Kang

Immune thrombocytopenia (ITP) is characterized by a low platelet count caused by immune-mediated platelet destruction. In children, ITP usually resolves on its own within three months, but treatment may be necessary in some cases. Beta-thalassemia (BT) is an inherited anemia caused by a deficiency in beta-globin protein chain synthesis, and its prevalence is increasing worldwide. Anemia is the most critical symptom, and its severity varies from mild to severe. Patients with BT typically have normal white blood cell (WBC) and platelet counts; however, in some cases, they may experience thrombocytosis or thromboembolic events. Thrombocytopenia is rare in patients with BT; however, some cases of ITP and BT co-occurrence have been reported in patients with thrombotic thrombocytopenic purpura (TTP). This report describes the case of a five-year-old girl diagnosed with BT who presented with immune thrombocytopenia and received rituximab.

Liam Murphy, John Shaker, Donal J. Buggy

Background: With the global disease burden of cancer increasing, and with at least 60% of cancer patients requiring surgery and, hence, anaesthesia over their disease course, the question of whether anaesthetic and analgesia techniques during primary cancer resection surgery might influence long term oncological outcomes assumes high priority. Methods: We searched the available literature linking anaesthetic-analgesic techniques and strategies during tumour resection surgery to oncological outcomes and synthesised this narrative review, predominantly using studies published since 2019. Current evidence is presented around opioids, regional anaesthesia, propofol total intravenous anaesthesia (TIVA) and volatile anaesthesia, dexamethasone, dexmedetomidine, non-steroidal anti-inflammatory medications and beta-blockers. Conclusions: The research base in onco-anaesthesia is expanding. There continue to be few sufficiently powered RCTs, which are necessary to confirm a causal link between any perioperative intervention and long-term oncologic outcome. In the absence of any convincing Level 1 recommending a change in practice, long-term oncologic benefit should not be part of the decision on choice of anaesthetic technique for tumour resection surgery.

E Orecchini, ML Belladonna, MT Pallotta et al.

Indoleamine 2,3 dioxygenase 1 (IDO1), a leader tryptophan-degrading enzyme, represents a recognized immune checkpoint molecule. In neoplasia, IDO1 is often highly expressed in dendritic cells infiltrating the tumor and/or in tumor cells themselves, particularly in human melanoma. In dendritic cells, IDO1 does not merely metabolize tryptophan into kynurenine but, after phosphorylation of critical tyrosine residues in the non-catalytic small domain, it triggers a signaling pathway prolonging its immunoregulatory effects by a feed-forward mechanism. We here investigated whether the non-enzymatic function of IDO1 could also play a role in tumor cells by using B16-F10 mouse melanoma cells transfected with either the wild-type Ido1 gene (Ido1WT) or a mutated variant lacking the catalytic, but not signaling activity (Ido1H350A). As compared to the Ido1WT-transfected counterpart (B16WT), B16-F10 cells expressing Ido1H350A (B16H350A) were characterized by an in vitro accelerated growth mediated by increased Ras and Erk activities. Faster growth and malignant progression of B16H350A cells, also detectable in vivo, were found to be accompanied by a reduction in tumor-infiltrating CD8+ T cells and an increase in Foxp3+ regulatory T cells. Our data, therefore, suggest that the IDO1 signaling function can also occur in tumor cells and that alternative therapeutic approach strategies should be undertaken to effectively tackle this important immune checkpoint molecule.

Z. Zholdybay, Z. Zhakenova, A. Ainakulova et al.

Relevance: The incidence of malignant neoplasms of various localizations is growing worldwide and in Kazakhstan. The mortality rate from oncological diseases is also alarmingly high. To facilitate early diagnosis and optimal therapy, scientists are exploring molecular diagnostics, including PET/CT, using various markers, like 18F-fluorodeoxyglucose, widely used in oncology but lacking specificity for certain types of tumors. The finding of Fibroblast Activation Protein (FAP) has sparked interest in FAP-targeted radiolabeled inhibitors (FAPI), which could serve as a universal marker for diagnosing different types of cancer. Various FAP markers for PET/CT are being studied, with special attention given to 68Ga-FAPI. The study aimed to analyze the potential value of FAPI PET/CT for detecting malignant tumors. Methods: A literature review was conducted using the MEDLINE, Embase, Scopus, PubMed, and Cochrane Central Register of Controlled Trials databases for the past decade using the following keywords: “malignant lesions,” “PET/CT,” and “FAPI.” This review analyzes 48 literАНДАТПА КЛИНИКАЛЫҚ ТӘЖІРИБЕДЕ 68GA-FAPI ПЭТ/КТ-НЫ ҚОЛДАНУ – ҚАТЕРЛІ ІСІКТЕРДІ ВИЗУАЛИЗАЦИЯЛАУ ПЕРСПЕКТИВАЛАРЫ: ӘДЕБИЕТКЕ ШОЛУ Ж.Ж. Жолдыбай1 , Ж.К. Жакенова1 , А.С. Айнакулова1,2, М.О. Габдуллина1 , Ж.М. Аманкулов2, Е.В. Филиппенко1 , Б.К. Исаматов1 , А.С. Алакова1 , Ю.Т. Дауытова1 1 «С.Д. Асфендияров атындағы Қазақ Ұлттық Медицина Университеті» КЕАҚ, Алматы, Қазақстан Республикасы; 2«Қазақ онкология және радиология ғылыми-зерттеу институты» АҚ, Алматы, Қазақстан Республикасы Өзектілігі: Әртүрлі локализациялардағы қатерлі ісіктермен сырқаттанушылық бүкіл әлемде де, Қазақстанда да өсуде. Онкологиялық аурулардан болатын өлім – жітім де жоғары. Ерте диагностика және оңтайлы терапия үшін ғалымдар молекулалық диагностиканы, соның ішінде әртүрлі маркерлерді қолданатын ПЭТ/КТ әдісін зерттейді. 18F-фтородезоксиглюкоза онкологияда кеңінен қолданылады, бірақ кейбір ісіктердің түрлерін нақты ажырата алмайды. Белсендіретін фибробластикалық ақуыздың (FAP) анықталуы әртүрлі қатерлі ісіктерді диагностикалаудың әмбебап маркері бола алатын FAP-бағытталған радио таңбаланған ингибиторларға (FAPI) қызығушылық тудырды. Қазіргі уақытта ПЭТ/КТ үшін әртүрлі FAP маркерлері зерттелуде, олардың арасында 68Ga-FAPI ерекше орын алады. Зерттеудің мақсаты – қатерлі ісіктерді анықтаудағы FAPI ПЭТ/КТ-ның мүмкіндіктерін талдау. Әдістері: MEDLINE, Embase, Scopus, PubMed Cochrane Central Register of Controlled Trials дерекқоры бойынша келесі түйінді сөздермен: "қатерлі ісіктер", "ПЭТ/КТ" және "FAPI" шолу жүргізілді. Бұл шолуда әртүрлі локализациялардағы ісіктерді анықтау, сатылау, емдеу тиімділігін қарастыруда 68Ga-FAPI ПЭТ/КТ-ның диагностикалық мүмкіндіктерін бағалауға арналған A1 дәлелдеу деңгейі бар 48 дереккөздің нәтижелері сипатталған. Нәтижелері: 68Ga-FAPI PET/CT маркерінің сезімталдығы мен өзгешелігі туралы мәліметтерді жинайтын жұмыстарды талдау келесі көрсеткіштерді айқындайды: сәйкесінше 95%-дан 100%-ға дейін және 62%-дан 100%-ға дейін. Алайда, тәжірибеде қолдануға нақты көрсеткіштерді қалыптастыру үшін 68Ga-FAPI ПЭТ/КТ-ның диагностикалық мүмкіндіктері әлі де қатысушылардың саны мен біртектілігін арттыра отырып қосымша зерттеулерді қажет етеді. Қорытынды: FAPI ПЭТ/КТ-ның диагностикалық мүмкіндіктері туралы деректерге шолу маркердің қатерлі ісік диагностикасында қолданылу әлеуетін көрсетеді. 68Ga-FAPI ПЭТ/КТ-ның көмегімен алынатын ақпарат ядролық медицинаның өзге маркерлары арқылы алынған мағлұматты толықтырады және науқастардың әрбір нақты жағдайдағы емдеу тактикасына әсер етеді. Түйінді сөздер: қатерлі ісіктер, ПЭТ/КТ, FAPI. Imaging analysis and histological validation // Radiother Oncol. – 2021. – Vol. 160. – P. 192-201. https://doi.org/10.1016/j.radonc.2021.04.016 42. Lai D., Ma L., Wang F. Fibroblast activation protein regulates tumorassociated fibroblasts and epithelial ovarian cancer cells // Int J Oncol. – 2012. – Vol. 41, №2. – P. 541-50. https://doi.org/10.3892/ijo.2012.1475 43. Hussain A., Voisin V., Poon S., Karamboulas C., Bui N.H.B., Meens J., Dmytryshyn J., Ho V.W., Tang K.H., Paterson J., Clarke B.A., Bernardini M.Q., Bader G.D., Neel B.G., Ailles L.E. Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21 // J Exp Med. – 2020. – Vol. 3, №217(8). – P. 234-243. https://doi. org/10.1084/jem.20191094 44. Kessel K., Seifert R., Weckesser M., Boegemann M., Huss S., Kratochwil C., Haberkorn U., Giesel F., Rahbar K. 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Kessler L., Ferdinandus J., Hirmas N., Bauer S., Dirksen U., Zarrad F., Nader M., Chodyla M., Milosevic A., Umutlu L., Schuler M., Podleska L.E., Schildhaus H.U., Fendler W.P., Hamacher R. 68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial // J Nucl Med. – 2022. – Vol. 63, №1. – P. 89-95. https:// doi.org/10.2967/jnumed.121.262096 47. Jin X., Wei M., Wang S., Wang G., Lai Y., Shi Y., Zhang Y., Yang Z., Wang X. Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT // J Nucl Med. – 2022. – Vol. 63, №2. – P. 212-217. https://doi.org/10.2967/jnumed.121.262134 48. Schmidkonz C., Rauber S., Atzinger A., Agarwal R., Götz T.I., Soare A., Cordes M., Prante O., Bergmann C., Kleyer A., Ritt P., Maschauer S., Hennig P., Toms J., Köhner M., Manger B., Stone J.H., Haberkorn U., Baeuerle T., Distler J.H.W., Agaimy A., Kuwert T., Schett G., Ramming A. Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging // Ann Rheum Dis. – 2020. – Vol. 79, №11. – P. 1485-1491. https://doi.org/10.1136/annrheumdis-2020-217408 ОБЗОРЫ ЛИТЕРАТУРЫ Онкология и Радиология Казахстана, №3 (69) 2023 71 Прозрачность исследования: Авторы несут полную ответственность за содержание данной статьи. Конфликт интересов: Авторы заявляют об отсутствии конфликта интересов. Финансирование: Данная статья подготовлена в рамках реализации научного проекта «Совершенствование ядерной медицины с внедрением инновационных технологий гибридной визуализации злокачественных опухолей», ИРН: AP19679719 (источник финансированмя МНиВО РК). Вклад авторов: вклад в концепцию – Жолдыбай Ж.Ж., Ж.К. Жакенова, Айнакулова А.С., Аманкулов Ж.М.; научный дизайн – Айнакулова А.С., Жолдыбай Ж.Ж.; исполнение заявленного научного исследования – Айнакулова А.С., Габдуллина М.О., Алакова А.С., Дауытова Ю.Т.; интерпретация заявленного научного исследования – Айнакулова А.С., Габдуллина М.О., Филиппенко Е.В.; создание научной статьи – Айнакулова А.С., Габдуллина М.О., Исаматов Б.К. Сведения об авторах: Жолдыбай Жамиля Жолдыбаевна – д.м.н., проф., зав. каф. «Визуальная диагностика», НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77772101612, e-mail: joldybay.j@gmail.com, ORCID ID: 0000-0003-0553-9016; Жакенова Жанара Кабдуалиевна – к.м.н., проф. каф. «Визуальная диагностика», НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77754983950, e-mail: jja18@yandex.ru, ORCID ID: 0000-0002-6764-6821; Айнакулова Акмарал Сериковна – PhD, доцент каф. «Визуальная диагностика», НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», врач лучевой диагностики отд. Радиологии и Ядерной медицины АО «Казахский научно-исследовательский институт онкологии и радиологии», Алматы, Республика Казахстан, тел. +77017242429, e-mail: ar89@list.ru, ORCID ID: 0000-0003-1773-5145; Габдуллина Мадина Оразайкызы (корреспондирующий автор) – кандидат PhD, ассистент каф. «Визуальная диагностика», НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77064095432, e-mail: madina.orazaykyzy@gmail.ru, ORCID ID: 0000-0003-4993-4747; Аманкулов Жандос Муктарович – PhD, зав. отд. Радиологии и Ядерной медицины АО «Казахский научно-исследовательский институт онкологии и радиологии», Алматы, Республика Казахстан, тел. +77013514213, e-mail: zh.amankulov@kaznmu.kz, ORCID ID: 0000-0001-7389-3119; Филиппенко Евгения Владимировна – ассистент каф. «Визуальная диагностика» НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77051916774, e-mail: eclips_90@mail.ru, ORCID ID: 0000-0002-7153-3002; Исаматов Бекжан Калибаевич – кандидат PhD, ассистент каф. «Визуальная диагностика», НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77078288351, e-mail: b.isamatov@mail.ru, ORCID ID: 0000-0002-5515-8468; Алакова Акерке Сериковна – резидент каф. «Визуальная диагностика», НАО «Казахский национальный медицинский уни-верситет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77780004158, e-mail: alako-va_akerke@mail.ru, ORCID ID: 0009-0006-4047-6267; Дауытова Юлдузхан Турехановна – PhD кандидат, ассистент каф. «Визуальная диагностика» НАО «Казахский Национальный Медицинский Университет имени С.Д. Асфендиярова», Алматы, Республика Казахстан, тел. +77077474580, e-mail: juldiz.dauytova@mail.ru, ORCID ID: 0000-0002-9411-7589. Адрес для корреспонденции: Габдуллина М.О., ул. Сатпаева 90/43, кв.31, Алматы 050046, Республика Казахстан. ature sources w

M. Vogelbaum, Gongbo Li, A. Heimberger et al.

Glioblastoma is the most common primary malignant brain neoplasm and it remains one of the most difficult-to-treat human cancers despite decades of discovery and translational and clinical research. Many advances have been made in our understanding of the genetics and epigenetics of gliomas in general; yet, there remains an urgent need to develop novel agents that will improve the survival of patients with this deadly disease. What sets glioblastoma apart from all other cancers is that it develops and spreads within an organ that renders tumor cells inaccessible to most systemically administered agents because of the presence of the blood-brain barrier. Inadequate drug penetration into the central nervous system is often cited as the most common cause of trial failure in neuro-oncology, and even so-called brain-penetrant therapeutics may not reach biologically relevant concentrations in tumor cells. Evaluation of the pharmacokinetics and pharmacodynamics of a novel therapy is a cornerstone of drug development, but few trials for glioma therapeutics have incorporated these basic elements in an organ-specific manner. Window-of-opportunity clinical trial designs can provide early insight into the biological plausibility of a novel therapeutic strategy in the clinical setting. A variety of window-of-opportunity trial designs, which take into account the limited access to treated tissue and the challenges with obtaining pretreatment control tissues, have been used for the initial development of traditional and targeted small-molecule drugs and biologic therapies, including immunotherapies and oncolytic viral therapies. Early-stage development of glioma therapeutics should include a window-of-opportunity component whenever feasible.

A. Al-Hadidi, Hannah N. Rinehardt, Pattamon Sutthatarn et al.

Xiaxia Man, Xiaolin Yang, Zhentong Wei et al.

Abstract Background CXCL1 belongs to a member of the ELR + CXC chemokine subgroups that also known as GRO-alpha. It has been recognized that several types of human cancers constitutively express CXCL1, which may serve as a crucial mediator involved in cancer development and metastasis via an autocrine and/or paracrine fashion. However, the expression pattern and clinical significance of CXCL1 in human uterine cervix cancer (UCC), as well as its roles and mechanisms in UCC tumor biology remains entirely unclear. Methods The expression and clinical significance of CXCL1 in UCC tissues was explored using immunohistochemistry and bioinformatics analyses. The expression and effects of CXCL1 in HeLa UCC cells were assessed using ELISA, CCK-8 and transwell assays. Western blotting experiments were performed to evaluate the potential mechanism of CXCL1 on malignant behaviors of HeLa UCC cells. Results The current study demonstrated that CXCL1 was expressed in HeLa UCC cells, PHM1-41 human immortalized cervical stromal cells, as well as cervical tissues, with UCC tissues having an evidently high level of CXCL1. This high level of CXCL1 in cancer tissues was notably related to poor clinical stages and worse survival probability, rather than tumor infiltration and patient age. In addition, CXCL1 expression was extremely correlated with CCL20, CXCL8 and CXCL3 cancer-associated chemokines expression. In vitro, the growth and migration abilities of HeLa cells were significantly enhanced in the presence of exogenous CXCL1. Gain-function assay revealed that CXCL1 overexpression significantly promoted growth and migration response in HeLa cells in both autocrine and paracrine manners. Finally, we found that CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes, and HeLa cell malignant behaviors derived from CXCL1 overexpression were further interrupted in the presence of the ERK1/2 blocker. Conclusion Our findings demonstrate the potential roles of CXCL1 as a promoter and a novel understanding of the functional relationship between CXCL1 and the ERK signaling pathway in UCC.

Moqing Liu, Rebecca Smith, Tiera Liby et al.

Abstract Background Resistance to HER2-targeted therapeutics remains a significant clinical problem in HER2+ breast cancer patients with advanced disease. This may be particularly true for HER2+ patients with basal subtype disease, as recent evidence suggests they receive limited benefit from standard of care HER2-targeted therapies. Identification of drivers of resistance and aggressive disease that can be targeted clinically has the potential to impact patient outcomes. Methods We performed siRNA knockdown screens of genes differentially expressed between lapatinib-responsive and -resistant HER2+ breast cancer cells, which corresponded largely to luminal versus basal subtypes. We then validated hits in 2-d and 3-d cell culture systems. Results Knockdown of one of the genes, INHBA, significantly slowed growth and increased sensitivity to lapatinib in multiple basal HER2+ cell lines in both 2-d and 3-d cultures, but had no effect in luminal HER2+ cells. Loss of INHBA altered metabolism, eliciting a shift from glycolytic to oxidative phosphorylative metabolism, which was also associated with a decrease in tumor invasiveness. Analysis of breast cancer datasets showed that patients with HER2+ breast cancer and high levels of INHBA expression had worse outcomes than patients with low levels of INHBA expression. Conclusions Our data suggest that INHBA is associated with aggressiveness of the basal subtype of HER2+ tumors, resulting in poor response to HER2-targeted therapy and an invasive phenotype. We hypothesize that targeting this pathway could be an effective therapeutic strategy to reduce invasiveness of tumor cells and to improve therapeutic response.

Logan Corey, Logan Corey, Julie Ruterbusch et al.

ObjectivesTo evaluate risk of a second cancer and associated survival times in United States women with diagnosis of cancer.MethodsThe Surveillance Epidemiology and End Results (SEER) database was queried for 2 cohorts of women aged 18 - 89 with either an index gynecologic or non-gynecologic cancer diagnosed between 1992 – 2017. Index cases were followed to determine if a second primary cancer was subsequently diagnosed; defined according to SEER multiple primary and histology coding rules. Standard Incident Ratios (SIR) and latency intervals between index diagnosis and second primary diagnosis were evaluated. Among those who developed a second primary cancer, median survival times from diagnosis of second primary cancer were also calculated.ResultsBetween 1992 – 2017, 227,313 US women were diagnosed with an index gynecological cancer and 1,483,016 were diagnosed with an index non-gynecologic cancer. Among patients with index gynecologic cancer, 7.78% developed a non-gynecologic subsequent primary cancer. The risk of developing any non-gynecologic cancer following an index gynecologic cancer was higher than the risk in the general population (SIR 1.05, 95% CI 1.04 - 1.07). Organs especially at risk were Thyroid (SIR 1.45), Colon and Rectum (SIR 1.23), and Urinary System (SIR 1.33). Among women diagnosed with an index non-gynecologic cancer, 0.99% were diagnosed with a subsequent gynecologic cancer. The risk of developing a gynecologic cancer following a non-gynecologic cancer was also elevated compared to the average risk of the general population (SIR 1.05, 1.03 - 1.07), with uterine cancer having the highest SIR of 1.13.ConclusionThe risk of a developing a second primary cancer and the corresponding survival time is based on the order and site of the index and subsequent cancer. Surveillance guidelines should be examined further to optimize survivorship programs.

Rary P Mony, Lakshmi K, Renu Sukumaran et al.

The classification of neuroendocrine neoplasms has evolved substantially over time but remains a topic of controversy and debate. Cytology has become one of the mainstays of diagnosis for these tumors, and the treatment may be entirely based on the FNA report.: This is a retrospective study which aims to describe the cytological features found in different groups of Neuroendocrine neoplasms. We have also tried to enumerate the not so typical features which we have seen in our cases. Cases of Neuroendocrine neoplasms diagnosed by cytology in the year 2018 were included in this study. The slides of these cases were retrieved, cytological features reviewed, and clinicopathological features evaluated. Histopathological correlation was done wherever possible. In this retrospective study, there were 43 cases which included FNA (n=38), Fluid cytology(n=3), Bronchial washings and Brushings(n=2). FNA sites included lung, cervical lymph nodes, scalp, liver, pancreas, and mesentery with the cytological diagnoses of Small cell carcinoma (n=22) Neuroendocrine tumor (n=7), Large cell Neuroendocrine carcinoma (n=3) and Poorly differentiated carcinoma with neuroendocrine features (n=11). Features that are of help include scanty cytoplasm, fine or coarse granular chromatin, nuclear moulding and streaking, cells adhering to vessels, inconspicuous nucleoli, nuclear debris in small cell carcinomas; larger cell size, a moderate amount of cytoplasm, coarse granular chromatin in large cell neuroendocrine carcinomas; uniformity of cell size, round to plasmacytoid cells with stippled chromatin and rosette formation in carcinoid tumors. The identification of neuroendocrine morphology in cytology specimens is crucial as this would be the initial step towards using the appropriate markers for confirmation, which in turn has got therapeutic and prognostic significance.

K. Laktionov, E. Artamonova, Tatiana Borisova et al.

Lung cancer has the highest morbidity rate among all malignant tumors in men and the highest mortality rate in men and women in Russia. In total, 49 145 new cases of lung cancer were registered (diagnosed) in Russia in 2019. The majority of cases are related to exogenic carcinogens and mainly tobacco smoke. For several decades surgical resection with preoperative cytotoxic therapy was an optimal approach for maximal cure rate. This year recommendations were updated with new strategies including adjuvant anti-PD-L1 atezolizumab following completion of chemotherapy in PD-L1 positive patients and osimertinib for EGFR mutated cases. For this moment available data suggest the increase in disease free survival. Strategic approach to treatment for inoperable patients varies according to the status of driver mutations. New approach includes pretreatment option of testing for a wide spectrum of alterations with NGS based panels. Significant changes were incorporated into treatment of ALK mutated NSCLC with two new options of brigatinib for TKI naive patients and lorlatinib for those who progress on second generation drugs. Treatment strategy for patients without activating mutations is based on PD-L1 status. Tsis year recommendations included atezolizumab as a new monotherapy option for patients with high depression of PD-L1. Also treatment options for pembrolizumab, nivolumab and atezolizimab were widened with prolonged treatment schedules.