Oncology Task Research Articles

The Proapoptotic Action of Pyrrolidinedione-Thiazolidinone Hybrids towards Human Breast Carcinoma Cells Does Not Depend on Their Genotype.

The development of new, effective agents for the treatment of breast cancer remains a high-priority task in oncology. A strategy of treatment for this pathology depends significantly on the genotype and phenotype of human breast cancer cells. We aimed to investigate the antitumor activity of new pyrrolidinedione-thiazolidinone hybrid molecules Les-6287, Les-6294, and Les-6328 towards different types of human breast cancer cells of MDA-MB-231, MCF-7, T-47D, and HCC1954 lines and murine breast cancer 4T1 cells by using the MTT, clonogenic and [3H]-Thymidine incorporation assays, flow cytometry, ELISA, and qPCR. The studied hybrids possessed toxicity towards the mentioned tumor cells, with the IC50 ranging from 1.37 to 21.85 µM. Simultaneously, these derivatives showed low toxicity towards the pseudonormal human breast epithelial cells of the MCF-10A line (IC50 > 93.01 µM). Les-6287 at 1 µM fully inhibited the formation of colonies of the MCF-7, MDA-MB-231, and HCC1954 cells, while Les-6294 and Les-6328 did that at 2.5 and 5 µM, respectively. Les-6287 suppressed DNA biosynthesis in the MCF-7, MDA-MB-231, and HCC1954 cells. At the same time, such an effect on the MCF-10A cells was significantly lower. Les-6287 induces apoptosis using extrinsic and intrinsic pathways via a decrease in the mitochondrial membrane potential, increasing the activity of caspases 3/7, 8, 9, and 10 in all immunohistochemically different human breast cancer cells. Les-6287 decreased the concentration of the metastasis- and invasion-related proteins MMP-2, MMP-9, and ICAM-1. It did not induce autophagy in treated cells. In conclusion, the results of our study suggest that the synthesized hybrid pyrrolidinedione-thiazolidinones might be promising agents for treating breast tumors of different types.

Automatic Detection of Distant Metastasis Mentions in Radiology Reports in Spanish.

A critical task in oncology is extracting information related to cancer metastasis from electronic health records. Metastasis-related information is crucial for planning treatment, evaluating patient prognoses, and cancer research. However, the unstructured way in which findings of distant metastasis are often written in radiology reports makes it difficult to extract information automatically. The main aim of this study was to extract distant metastasis findings from free-text imaging and nuclear medicine reports to classify the patient status according to the presence or absence of distant metastasis. We created a distant metastasis annotated corpus using positron emission tomography-computed tomography and computed tomography reports of patients with prostate, colorectal, and breast cancers. Entities were labeled M1 or M0 according to affirmative or negative metastasis descriptions. We used a named entity recognition model on the basis of a bidirectional long short-term memory model and conditional random fields to identify entities. Mentions were subsequently used to classify whole reports into M1 or M0. The model detected distant metastasis mentions with a weighted average F1 score performance of 0.84. Whole reports were classified with an F1 score of 0.92 for M0 documents and 0.90 for M1 documents. These results show the usefulness of the model in detecting distant metastasis findings in three different types of cancer and the consequent classification of reports. The relevance of this study is to generate structured distant metastasis information from free-text imaging reports in Spanish. In addition, the manually annotated corpus, annotation guidelines, and code are freely released to the research community.

Upregulation of RSPO3 via targeted promoter DNA demethylation inhibits the progression of cholangiocarcinoma

BackgroundCholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research.ResultsOur study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression.ConclusionsOur findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA.

Multi-modal medical Transformers: A meta-analysis for medical image segmentation in oncology

Multi-modal medical image segmentation is a crucial task in oncology that enables the precise localization and quantification of tumors. The aim of this work is to present a meta-analysis of the use of multi-modal medical Transformers for medical image segmentation in oncology, specifically focusing on multi-parametric MR brain tumor segmentation (BraTS2021), and head and neck tumor segmentation using PET-CT images (HECKTOR2021). The multi-modal medical Transformer architectures presented in this work exploit the idea of modality interaction schemes based on visio-linguistic representations: (i) single-stream, where modalities are jointly processed by one Transformer encoder, and (ii) multiple-stream, where the inputs are encoded separately before being jointly modeled. A total of fourteen multi-modal architectures are evaluated using different ranking strategies based on dice similarity coefficient (DSC) and average symmetric surface distance (ASSD) metrics. In addition, cost indicators such as the number of trainable parameters and the number of multiply-accumulate operations (MACs) are reported. The results demonstrate that multi-path hybrid CNN-Transformer-based models improve segmentation accuracy when compared to traditional methods, but come at the cost of increased computation time and potentially larger model size.

Beyond the NURSE Acronym: The Functions of Empathy in Serious Illness Conversations.

Empathic communication, defined as both responding to emotions and actively appreciating another's world view, is associated with better outcomes for patients and families, including decreased anxiety and depression, and improved coping 1 Kelley JM Kraft-Todd G Schapira L Kossowsky J Riess H. The influence of the patient-clinician relationship on healthcare outcomes: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2014; 9: e94207https://doi.org/10.1371/journal.pone.0094207 Crossref PubMed Scopus (420) Google Scholar , 2 Hoffstädt H Stouthard J Meijers MC et al. Patients’ and Clinicians’ Perceptions of Clinician-Expressed Empathy in Advanced Cancer Consultations and Associations with Patient Outcomes. Palliative Medicine Reports. 2020; 1: 76-83https://doi.org/10.1089/pmr.2020.0052 Crossref Google Scholar , 3 Neumann M Wirtz M Bollschweiler E et al. Determinants and patient-reported long-term outcomes of physician empathy in oncology: a structural equation modelling approach. Patient Educ. Couns. 2007; 69: 63-75https://doi.org/10.1016/j.pec.2007.07.003 Crossref PubMed Scopus (186) Google Scholar , 4 Flickinger TE Saha S Roter D et al. Clinician empathy is associated with differences in patient-clinician communication behaviors and higher medication self-efficacy in HIV care. Patient Educ. Couns. 2016; 99: 220-226https://doi.org/10.1016/j.pec.2015.09.001 Crossref PubMed Scopus (68) Google Scholar , 5 Hojat M Louis DZ Markham FW Wender R Rabinowitz C Gonnella JS. Physicians’ empathy and clinical outcomes for diabetic patients. Acad. Med. 2011; 86: 359-364https://doi.org/10.1097/ACM.0b013e3182086fe1 Crossref PubMed Scopus (678) Google Scholar . Despite this, clinicians who have not undergone formal communication training typically focus on information exchange and miss patients’ emotional and social cues. To address this gap, we use the acronym NURSE (Name, Understand, Respect, Support, Explore) 6 Fortin AH Dwamena FC Frankel RM Smith RC Smith's Patient-Centered Interviewing : An Evidence-Based Method. 4th ed. McGraw-Hill Education, New York2019 Google Scholar ,7 Back AL Arnold RM Baile WF Tulsky JA Fryer-Edwards K. Approaching difficult communication tasks in oncology. CA Cancer J Clin. 2005; 55: 164-177https://doi.org/10.3322/canjclin.55.3.164 Crossref PubMed Scopus (430) Google Scholar to teach trainees how to respond to patient emotions. When used effectively, these skills communicate caring and help patients and families navigate their emotions and cope with their circumstances, both of which ultimately help with decision-making. However, we worry that some learners may not progress beyond this model, and may even see these empathic statements as a tool to get emotions to settle down and let the patient can make the “right” decision. This suggests that we - the teachers - need to do a better job explaining the way that emotions and empathy function in the clinician-patient/family interaction. Emotion and decision-making theory 8 Lerner JS Li Y Valdesolo P Kassam KS. Emotion and decision making. Annu. Rev. Psychol. 2015; 66: 799-823https://doi.org/10.1146/annurev-psych-010213-115043 Crossref PubMed Scopus (1081) Google Scholar ,9 Conte B Hahnel UJJ Brosch T. From values to emotions: Cognitive appraisal mediates the impact of core values on emotional experience. Emotion. 2022; https://doi.org/10.1037/emo0001083 Crossref Scopus (1) Google Scholar , as well as our clinical experiences, lead us to conclude that skilled empathy, beyond resolving emotion so the conversation can move forward, helps us in these discussions in at least four additional ways. Empathy helps us uncover and understand patient values, to appropriately pace the conversation, to facilitate healthy grieving, and, ultimately, transforms how we approach our work. Below we describe these four functions of empathy in an encounter in which we meet with a patient with serious illness or their family to discuss medical decisions. . We focus on the hospital setting, where we meet families in crisis and must build a connection quickly. However, these skills may apply to a wide variety of clinical encounters.

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers.

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

Enhancing an Oxidative "Trojan Horse" Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside.

The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative "Trojan horse" agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC's non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.

Intracytoplasmic Trafficking of Nanoparticles based on Hyaluronic Acid and Chitosan for Targeted Delivery of Anticancer Drugs

Cancer diseases are characterized by high incidence and mortality worldwide. The main problem in cancer therapy is the lack of specificity of anti-cancer drugs. Therefore, the development of new methods of targeted delivery of anti-cancer drugs is an urgent task in oncology. Nanoparticles from hyaluronic acid and chitosan (HA:CS) were obtained using ionotropic gelation technology. The size of the nanoparticles was investigated using dynamic light scattering. Nanoparticles were obtained of a size of 100-400 nm. A physical association method has been developed for encapsulating nanoparticles with doxorubicin, a well-known antitumor drug, and dinitrosyl iron complex (DNIC; donor of nitric oxide). Using the method of dynamic light scattering, the surface potential of nanoparticles was measured. It was found that the resulting nanoparticles (HA-DOX:CS) were stable and had a surface potential of -45.6 meV. Using the method of confocal and FLIM microscopy, the localization of nanoparticles in cancer cells was studied. These methods have shown that nanoparticles pass through the cytoplasmic membrane and are localized inside the cells. It was also shown that nanoparticles (HA:CS-Rhod) were localized in the cytoplasm of African green monkey renal epithelial cells. It was found that the incorporation of DNIC into the composition of nanoparticles significantly increased the stability of DNIC, while prolonging the formation time and increasing the yield of nitric oxide. Thus, we have developed unique nanoparticles for the targeted delivery of antitumor drugs into cells.

Hypoxia-related proteins VEGF A and CA IX and resistance of soft tissue sarcoma cells to chemotherapy: <i>ex vivo</i> pilot study

Introduction. The identification of predictive factors is a cornerstone task of modern oncology. The development of new targeted drugs determines the need for prediction of chemosensitivity of each patient to the prescribed therapy, in this regard, the search for biomarkers of predictive response to therapy is actively conducted.The study objective to investigate the relationship between tumor cell resistance and the expression levels of CA IX (carbonic anhydrase IX) and VEGF A (vascular endothelial growth factor А) in patient-derived cultures of soft tissue sarcomas.Materials and methods: ex vivo soft tissue sarcoma cell culture, resazurin test, immunoblotting.Results. We obtained 46 ex vivo samples of soft tissue sarcoma cultures for which chemosensitivity to doxorubicin, ifosfamide, docetaxel, gemcitabine, and their combinations was assessed by the resazurin cytotoxicity test. We analyzed the relationship between the expression of hypoxic proteins VEGF A and CA IX and the resistance to drugs. A correlation between the CA IX expression in hypoxia and cell resistance to ifosfamide and its combination with doxorubicin was found. Soft tissue sarcomas with high VEGF A index were resistant to doxorubicin, docetaxel, and its combination with gemcitabine (p <0.05).Conclusion. The data obtained on patient-derived cultures indicate the relationship between hypoxic signaling and resistance of soft tissue sarcomas to chemotherapeutics.

The need for artificial intelligence curriculum in medical education: A Canadian cross-sectional study of future oncology trainees.

e13583 Background: Emerging artificial intelligence (AI) technologies have diverse applications in medicine, with early evidence suggesting that AI tools can accurately perform key tasks in oncology. As AI tools advance towards clinical implementation, skills in how to use and interpret AI in a healthcare setting could become integral for physicians. This study seeks to assess exposure to AI in medical education among trainees interested in pursuing a career in oncology, and the need for AI education in medicine. Methods: A 32 question survey for Canadian undergraduate medical students was distributed to students at all 17 Canadian medical schools. The survey assessed the currently available and perceived need for learning opportunities about AI and barriers to educating about AI in medicine. Interviews were conducted with participants to provide narrative context to survey responses. Likert scale (LS) survey questions were scored from 1 (disagree) to 5 (agree), and analyzed using a two-sided one sample t-test vs a neutral value. Interview transcripts were analyzed using qualitative thematic analysis. Results are described as mean LS score ± standard deviation. Results: We received 486 responses from 17 of 17 medical schools. Of these respondents, 98 (20.2%) are willing to pursue a residency in an oncology-related field (pathology, radiology, general surgery, internal medicine, radiation oncology). Respondents agreed that AI applications in medicine would become common in the future (3.80±0.38) and would improve medicine (3.71±0.54). Further, respondents agreed that they would need to use and understand AI during their medical careers (3.76±0.572; 3.43±0.773), and that AI should be formally taught in medical education (3.43±0.756). In contrast, a significant number of participants indicated that they did not have any formal educational opportunities about AI (1.76±0.785) and that AI-related learning opportunities were inadequate (2.12±0.802). Interviews with 18 students were conducted. Emerging themes from the interviews were a lack of formal education opportunities and logistical challenges in adding AI to curriculum. Conclusions: A lack of educational opportunities about AI in medicine were identified across Canadian medical students. Given that medical students overwhelmingly believe that AI is important to the future of medicine, and AI tools are currently progressing towards clinical implementation, AI should be considered for inclusion in formal medical curriculum.

Circulating microRNA: Searching for new players in assessment of therapy response in colorectal cancer patients.

183 Background: The identification of clinicopathological and molecular predictive and/or prognostic factors represents currently one the most challenging tasks in oncology. Significant efforts are currently being dedicated to identify patients who will or will not benefit from chemotherapy. In fact, drug resistance is a limiting factor of the efficacy of chemotherapy in colorectal cancer (CRC) treatment. However, despite modern surgical techniques and adjuvant systemic therapy, only 20% of patients with distant metastasis achieve long-term remission, while 60–70% of patients develop local or distant recurrence. Methods: Recently, we have identified by high-throughput approach that circulating microRNAs (miRNAs), namely, miR-122-5p and miR-142-5p show a high potential for CRC screening and early detection as well as for the assessment of patients’ outcomes and the effectiveness of treatment schedule. Results: In detail, the expression levels of these miRNAs were significantly different between CRC patients and controls. A year after diagnosis, miRNA expression profiles were significantly modified in patients responding to treatment and were no longer different from those measured in controls. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling. As selection during metastasizing may shift molecular patterns by which CRC liver metastases retain their unique molecular profile, we thus elaborated our results on CRC patients with liver metastasis and measured these circulating miRNAs repeatedly over two years. The first sampling was performed at the time of post therapy developed liver metastasis (i.e., recurrence), and every 3 months depending on patients` conditions (i.e., covering the liver resection, administration of chemotherapy etc). Detailed results of the study will be presented during the meeting. Conclusions: The present study aimed to explain why patients with the same cancer stage may differ in treatment susceptibility and long-term outcomes.

The role of modern methods of nuclear medicine in the diagnosis of radiation disease in patients after radiation and radionuclide therapy

The review considers the effectiveness of modern methods of nuclear medicine in the diagnosis of radiation disease to normal tissues in patients after radiation and radionuclide therapy. At the present stage, the assessment of radiation disease in the use of radiation and radionuclide therapy using nuclear medicine is one of the priority tasks in oncology. Hybrid methods of nuclear medicine have the ability to objectively identify and evaluate high-resolution radiation disease to normal tissues in order to predict and monitor the effects of radiation and radionuclide therapy on them. Key words: radiation disease, nuclear medicine, radiation therapy, radionuclide therapy.

Остеопонтин та остеокальцин при раку легенів

Актуальність. Рак легенів (РЛ) займає лідуючу позицію в структурі онкологічної захворюваності та є однією з провідних причин смерті від онкозахворювань. Пошук ефективних підходів до оцінки перебігу РЛ з використанням інформативних критеріїв є актуальним завданням сучасної онкології. РЛ зазвичай перебігає з підвищеним рівнем у крові остеопонтину (ОР) та остеокальцину (ОС), що має прогностичну значущість у рамках виживання хворих. Сироватковий вміст цих остеоонкомаркерів прямо асоціюється з наявністю у хворих метастазів і з високими темпами прогресування захворювання, але ці дані вимагають подальшого уточнення. Мета дослідження: оцінити клініко-патогенетичну й прогностичну значущість ОР та ОС у хворих із різними варіантами перебігу РЛ. Матеріали та методи. Обстежено 115 хворих на РЛ віком від 24 до 80 років (у середньому 58 років), серед яких було 78 % чоловіків і 22 % жінок. Жоден пацієнт раніше не був прооперований із приводу РЛ і до обстеження не отримував радіохіміотерапію. Дрібноклітинний гістологічний варіант РЛ встановлений у 17 % від числа хворих, недрібноклітинний — у 83 %. Імуноферментним аналізом вивчали в сироватці крові показники ОР, ОС і судинного ендотеліального фактору росту (VEGF). Результати. У хворих на РЛ збільшуються в сироватці крові показники онкоостеоасоційованих маркерів OP та OC, що спостерігається відповідно в 99 і 98 % випадків. Зміни ОР і ОС пов’язані з формою захворювання, гістологічним його варіантом, ступенем диференціації, інтегральною тяжкістю перебігу РЛ, характером ускладнень первинної пухлини й особливостями метастазування. Високий рівень маркерів у крові мало впливає на трирічне виживання пацієнтів, а прогнознегативними критеріями відносно перебігу РЛ є параметри ОР. Показники ОР і ОС у крові між собою прямо корелюють, а вміст ОР, окрім того, має позитивні співвідношення з таким пухлинним маркером, як VEGF, що належить до стимуляторів неоангіогенезу. Метастатичне ураження скелету й розвиток порушень мозкового кровообігу внаслідок подальшої радіохіміотерапії прямо пов’язані з високою концентрацією в крові ОР, який також є чинником ризику інших ускладнень лікування. Висновки. Підвищені рівні в крові ОР і ОС мають важливе клініко-патогенетичне значення при РЛ, а вивчення показників цих остеоонкомаркерів сприятиме ранній діагностиці окремих ознак перебігу захворювання, підвищенню якості оцінки метастазування в кістково-суглобовий апарат і прогнозуванню можливих ускладнень радіохіміотерапії.

Antimetastatic effect of organotin compounds on the model of melanoma B16 in the experiment.

e21564 Background: Melanoma is an extremely malignant tumor. The unfavorable prognosis in the treatment of patients is mainly due to aggressive metastasis of the tumor in various ways: hematogenic, lymphogenic and lymphohematogenic. Metastatic melanoma cells are relatively drug - resistant. Despite some successes in the treatment of melanoma, the search for new antimetastatic substances remains an urgent task of experimental pharmacology and oncology. Organotin compounds were studied by us as promising candidates for antimetastatic agents. Methods: The study was conducted on experimental C57BL/6 mice (n =72, each cohort contained 12 mice) with B16 melanoma (subcutaneous transplantation) to determine the intensity of metastasis in the presence of the cytotoxic organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) [1-3] (Me3). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Female mice (8 weeks of age, weighing 21-22 g) were administered intraperitoneal 1% aqueous gelatin solution of organotin Me3 daily for 5 days. The total doses in the first series of the experiment were 150, 250, 375 mg/kg (I, II, III cohorts and IV control group), which allowed us to choose the most effective dose of Me3. After that, in the second series of experiments, the metastasis inhibition index was evaluated in group V (total dose 375 mg/kg) and control group VI. The animals were euthanized on the 18th day after the tumor was inoculated. Results: It was shown that when administered intraperitoneal to mice, Me3 did not inhibit the growth of B16 melanoma in any of the groups. The results showed that the average life expectancy of animals in the experimental group III with the introduction of Me3 at a dose of 375 mg/kg significantly increased and amounted to 30.1±2.5 days, in control mice of group IV-21.8±2.6 days. In the second series of the experiment, after 18 days, the index of metastasis inhibition was almost twice lower (54%) in group V than in the control group (VI). Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) (Me3) is an effective antimetastatic agent in transplanted experimental mouse melanoma B16 at a total dose of 375 mg/kg.

Репродуктивная функция у лиц, излеченных от онкологических заболеваний

Modern cancer therapy programs allow an increasing number of patients to be cured, and therefore the quality of their subsequent life is an important task of clinical oncology. The ability to realize reproductive potential is one of the main criteria for the quality of life. Nevertheless, chemoradiation therapy used in the treatment of malignant tumors can cause temporary or permanent infertility. Currently, there are options to protect the reproductive system from chemoradiation treatment (administration of ethinylestradiol drugs, gonadotropin-releasing hormone agonists) or harvesting seminal fluid/oocytes, and cryopreservation of ovarian tissue. However, the low awareness of doctors about modern reproductive technologies in the treatment of persons cured from cancer leads to the fact that these methods are not used actively enough. The article presents the main chemotherapy drugs used in the treatment of malignant tumors that can cause an impairment of reproductive function; describes their pathological effects on oocytes and spermatozoa; provides methods of protecting the reproductive function in persons who take chemoradiation therapy or have completed antitumor therapy.

Implementation science of district cancer care delivery model (Pendharkar model).

e19024 Background: Health care systems are fighting with issues related to multiple elements of access to care. The problems include non availability of physical facilities and qualified human resource. Here we report successful intervention results of a scalable, replicable, cancer care model starting with two and expanding to nearly 198 districts, using standard processes. This has brought specialised cancer care to government run general district hospitals using existing human resource, through empowerment of alternate oncology workforce, capacity building, decentralisation, and task sharing with impactful outcome. Methods: Government run general district hospitals were involved to train one physician and nurse in principles of oncology care over one month period, followed by constant 24 x7 support and continued training etc. (techno-mentoring). Administrative changes enabled creation of identity of nodal cancer units and organised process of cancer drug delivery. Results: The implementation process was experimented in two hospitals and later on extended to nearly 198 hospitals, over a period of six years (Table). Majority of states have formulated the innovation as state run district cancer care program with published operational guidelines. The state governments designated physicians as nodal cancer officers and created their identity with physical allocation of space and providing cancer drug formulary. The physicians are assisting cancer patients from diagnosis up to end of life care including chemotherapy, palliative care. More then 45000 patients have availed services. Few thousand chemotherapy sessions have been performed by alternate oncology workforce. Drug availability is maintained through routine government supplies by adding anticancer drugs to list of essential medicines. Satisfaction survey conducted amongst patients, has proved its usefulness, acceptability. Conclusions: Impactful implementation at scale is feasible for cancer care delivery, using existing physical infrastructure and empowerment of alternate oncology workforce, through this model. It can ideally serve areas with no access to cancer care, including LMIC. [Table: see text]

IMMUNOLOGICAL CHANGES IN PATIENTS WITH MALIGNANT TUMORS AFTER CRYOGENIC AND ULTRASONIC ABLATION OF A TUMOR

Studies on experimental animal models and clinical trials indicate that cryosurgery of tumor focus leads to the activation of antitumor immunity. Systematic minimally invasive surgical impact on the primary tumor or its metastases, causing a pronounced immune response, becomes an actual task of modern oncology.

Functional Activity of Ehrlich Carcinoma Cancer Stem Cells After Treatment By Orthovanadate-Based Nanoparticles

ABSTRACT Aim: Development of tumors results from the expansion of cancer stem cells (CSCs) population. The application of nanocomposites capable of CSCs visualization, binding with them and inducing tumor destruction is a prospective task in oncology. This research aimed to study the CSCs' functional activity as a part of Ehrlich's adenocarcinoma (EAC) after incubation with orthovanadate-based nanoparticles. Methods: Experiments were implemented in Balb/C mice with experimental induction of EAC. The EAC cells were cultured for 7 days in the peritoneal cavity (PC) of mice prior to and after incubation with nanoparticles (NP) of different forms and concentrations. The methods for procurement of aqueous colloid solutions of orthovanadate-based NP were described [Klochkov V.K., 2009]. Luminescence spectra of EAC cells after incubating with NP were analyzed with monochromator MDR-23. The intensity of EAC development was determined by the volume of ascitic fluid in PC taking cell concentration into account. EAC cells after incubation with NP were visualized in luminescent microscope Olympus IX 71; cells with phenotype CD44hi, CD44+CD24-, CD44+CD24+, CD44-CD24+, CD117+, Sca-1+ were analyzed with flow cytometer (Facs Calibur); the level of nanog gene expression was assessed with RT-PCR. Results: According to data from luminescent microscopy only NP of spherical shape demonstrated the capability of visualizing EAC cells. In this case all the types of NP inhibited tumor growth to different extents. The highest inhibition of tumor growth and nanog gene expression was established using spindle-like NP. Conclusions: We demonstrated here the capability of certain shapes of orthovanadate-based synthesized NP to inhibit EAC growth, that may be further used in clinical practice for therapy of oncological diseases. Disclosure: All authors have declared no conflicts of interest.

Ärztliche Behandlung von an Krebs Erkrankten – Alles ganz anders?

Cancer deaths contribute to more than 25% of the overall mortality in Germany, which is only superseded by death from cardiovascular diseases. Apart from improving cancer prevention, the development of effective therapies for advanced cancer is a key task in oncology. Here we compare the criteria of clinical effectiveness that are applied to medical cancer therapies with those that are applied to therapies for cardiovascular diseases. (As supplied by publisher).

Frédéric Amant: leading the agenda on cancer in pregnancy

Frédéric Amant: leading the agenda on cancer in pregnancy