Hematogenous Metastasis Research Articles

Value of Clinical Information on Radiology Reports in Oncological Imaging.

Radiological reporting errors have a direct negative impact on patient treatment. The purpose of this study was to investigate the contribution of clinical information (CI) in radiological reporting of oncological imaging and the dependence on the radiologists’ experience level (EL). Sixty-four patients with several types of carcinomas and twenty patients without tumors were enrolled. Computed tomography datasets acquired in primary or follow-up staging were independently analyzed by three radiologists (R) with different EL (R1: 15 years; R2: 10 years, R3: 1 year). Reading was initially performed without and 3 months later with CI. Overall, diagnostic accuracy and sensitivity for primary tumor detection increased significantly when receiving CI from 77% to 87%; p = 0.01 and 73% to 83%; p = 0.01, respectively. All radiologists benefitted from CI; R1: 85% vs. 92%, p = 0.15; R2: 77% vs. 83%, p = 0.33; R3: 70% vs. 86%, p = 0.02. Overall, diagnostic accuracy and sensitivity for detecting lymphogenous metastases increased from 80% to 85% (p = 0.13) and 42% to 56% (p = 0.13), for detection of hematogenous metastases from 85% to 86% (p = 0.61) and 46% to 60% (p = 0.15). Specificity remained stable (>90%). Thus, CI in oncological imaging seems to be essential for correct radiological reporting, especially for residents, and should be available for the radiologist whenever possible.

Invasive Orbital Squamous Cell Carcinoma in a Patient with Multiple Myeloma

Background Orbital squamous cell carcinoma (SCC) is a rare entity. It is often a result of local invasion of SCC originating from the skin, nasopharynx, nasal cavity, paranasal sinuses, conjunctiva, lacrimal glands, or sac or less commonly occurs through hematogenous metastasis. Herein, we report a patient with orbital SCC with a history of multiple myeloma (MM). Case presentation. A 45-year-old woman with a history of MM in the past two years presented to our clinic complaining of gradual right eye proptosis for six months. The relative afferent pupillary defect was detected in the right eye on her examination. Ocular movements of the right eye were limited in all directions. Orbital magnetic resonance imaging demonstrated an infiltrative mass in the right orbit extended from the anterior to the orbital apex and the optic canal. The patient underwent debulking, and a histopathology examination revealed SCC results. No other secondary site was found to be the origin of the tumor. Result The patient underwent chemotherapy and subsequent radiotherapy. To our knowledge, this is the first report of concomitant MM and primary orbital SCC.

Amphicrine Medullary Thyroid Carcinoma - a Case-Based Review Expanding on Its MUC Expression Profile.

Amphicrine phenotype in medullary thyroid carcinoma (MTC) is a rare phenomenon characterized by tumor cells that show both endocrine differentiation (calcitonin secretion) and exocrine differentiation (mucin production and secretion). Not much is known about the pathobiology of amphicrine MTCs. This report undertook a case-based review approach by discussing the cytological, histopathological, and ultrastructural features of this rare enigmatic entity, expanding on the radiological and novel MUC immunohistochemistry findings from a 28-year-old MEN2B syndrome patient with C cell hyperplasia and multifocal MTC with amphicrine features. The patient had widespread hematogenous metastases at presentation. MUC immunoexpression analysis revealed evidence of micro-lumina formation, and unique to-date unreported expression patterns of MUC1, MUC5AC, and MUC6 in an amphicrine subtype of MTC. Review of the literature identified five other MTC cases with well-documented amphicrine features. Of these six cases, two were associated with MEN2B syndrome, and four had metastatic disease. Follow-up was available in three patients, and two died of disease. Recognition of this rare subtype of MTC may be of clinical interest given their frequent link to MEN2B syndrome and biological aggressiveness.

Pancreatic metastases from uterine cervix tumors – diagnostic challenge and therapeutic options

Pancreatic metastases represent rare eventualities, being more frequently encountered in colorectal, ovarian or breast cancer, other primaries being usually reported more often in autopsy studies. When it comes to cervical cancer, it usually is responsible for the development of local recurrences, lymphatic recurrences or hematogenous metastases in lungs. The aim if the current paper is to discuss about the possibility of developing pancreatic metastases from cervical cancer and to analyze the most efficient therapeutic strategies in such cases.

Abstract 5548: PB101 simultaneously targets tumor angiogenesis and immunity and enhances the efficacy of PD-L1 immune checkpoint blockade

Abstract Introduction: Tumor vasculature plays an important role in promoting tumor progression and immune evasion. Previously, we developed PB101, a novel glycosylated decoy receptor that can neutralize VEGF-A, VEGF-B, and PlGF, and demonstrated that it potently inhibits tumor angiogenesis, thereby retarding tumor growth and metastasis. However, its impact on tumor microenvironment (TME), especially anti-cancer immunity, has not been fully elucidated. Here, we investigated distinct modes of immune modulation by PB101 compared with other anti-angiogenic agents, and evaluated its immunotherapeutic potential when combined with immune checkpoint inhibitors (ICIs). Methods: MC38 colon or Hepa-V liver cancer-bearing mice were treated with PB101 or other anti-angiogenic agents with or without various ICIs. The TME was evaluated by histologic, flow cytometric, and Nanostring immune profiling analyses. Results: PB101 markedly suppressed MC38 colon and Hepa-V liver cancer growth in vivo. It simultaneously inhibited both VEGF and PlGF signaling within the TME, thus suppressing tumor angiogenesis. PB101 also induced extensive immune remodeling of the TME. PB101 enhanced intratumoral dendritic cells, but reduced M2-like tumor-associated macrophages. Moreover, PB101 resulted in high influx of activated CD8+, but not CD4+, T cells into the TME. PB101 exhibited the most prominent immune-modulating effect compared with other vascular targeting agents. When combined with various ICIs, PB101 had the greatest synergism with anti-PD-L1 antibody, inducing complete tumor regression and long-term survival. Furthermore, PB101-based combination immunotherapy induced a durable and protective immunity against subcutaneous tumor re-challenge and hematogenous lung metastasis. Conclusion: PB101 elicited strong anti-tumor immunity more effectively than other anti-angiogenic agents. PB101 can strengthen the immunotherapeutic efficacy of PD-L1 inhibitor by establishing a potent and durable immune memory. The combination of PB101 and PD-LI needs to be further validated in clinical trials. Citation Format: Hannah Yang, Seung Joon Lee, Hyun-Gul Yang, Won Suk Lee, Jaekyung Cheon, Beodeul Kang, Sung-Eun Kim, Hyeseong Lim, Hong Jae Chon, Chan Kim. PB101 simultaneously targets tumor angiogenesis and immunity and enhances the efficacy of PD-L1 immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5548.

Abstract 259: Study of a low anticoagulant bovine heparin as a drug capable of disrupting tumor cell-platelet interaction and preventing hematogenous metastasis

Abstract Metastasis is the leading cause of death in cancer patients. During metastatic dissemination, circulating tumor cells need to survive in the bloodstream and their interaction with platelets through P-selectin-ligand seems to be crucial. It has been demonstrated that heparin (from porcine mucosa, porcine UFH), a glycosaminoglycan composed by repetitive disaccharides of uronic acid and glucosamine, may interfere with P-selectin interaction. Recently our research group purified by ion exchange chromatography a fraction of bovine heparin displaying very low anticoagulant potential, named LABH (~20 IU/mg LABH x ~200 IU/mg porcine UFH x ~100 IU/mg bovine UFH). The advantage of bovine UFH and, especially of LABH, is their reduced risk of bleeding side effect. Our aim in this work was to investigate the potential use of LABH as an antimetastatic agent in vitro and in vivo, evaluating its ability to interfere with tumor cell-platelet interaction, tumor cell binding to P-selectin and preventing induced metastasis in mice. For this, we challenged 8-12 weeks C57Bl/6 mice with 4 or 8 mg/kg of porcine UFH, bovine UFH or LABH followed by intravenous injection of B16F10 cells (murine melanoma cell line). After 21 days, lungs were analyzed and metastatic foci were counted. The number of metastatic foci was significantly reduced when animals were pretreated with heparins (50-70 foci in control mice and 10-15 in treated mice). In other attempt, isolated platelets from healthy volunteers were incubated for 1h with MV3 cells (human melanoma cell line) in vitro in the presence or absence of heparin. All three heparins tested were efficient in blocking MV3-platelet interaction in a dose-response manner, but LABH required higher doses than porcine and bovine UFH. When analyzing the direct binding of U937 cell (human lymphoma cell line) to immobilized P-selectin, we could observe that porcine and bovine UFH inhibited at the same level (~ 60% of inhibition with 100 μg/mL), while LABH was less effective (~ 45% of inhibition with 100 μg/mL). Collectively our results demonstrate that despite presenting distinct patterns of sulfation and anticoagulant potential, all heparins significantly reduced lung metastasis, platelet-tumor cell adhesion and P-selectin binding. On the other hand, we hypothesize that LABH may act suppressing metastasis also by other mechanisms since its effect on in vitro experiments was less pronounced in comparison to porcine and bovine UFH. Citation Format: Juliana Maria Motta, Carlos Roberto-Fernandes, Kayene Vitória Micheli, Ana Maria Tovar, Paulo Antônio Mourão, Mariana Sá Pereira. Study of a low anticoagulant bovine heparin as a drug capable of disrupting tumor cell-platelet interaction and preventing hematogenous metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 259.

Abstract 5669: Distinct genetic features between osteosarcomas firstly metastasizing to bone and to lung

Abstract Background Osteosarcoma (OS) is a highly aggressive malignant tumor of mesenchymal origin and prone to early hematogenous metastases. The 5-year overall survival of metastatic OS is only approximately 20% to 30%. Therefore, it is still clinical dilemma in the treatment of OS. Thus,understanding the molecular features of metastatic osteosarcoma become increasingly important. Methods Formalin-fixed, paraffin-embedded or fresh tissues and matched blood samples were collected from OS patients for whole exome sequencing using next-generation sequencing at OrigiMed (Shanghai, China), a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Genomic alterations including single nucleotide variations (SNVs), short and long insertions/deletions (INDELs), copy number variations (CNVs), and gene rearrangements were assessed. Tumor mutational burden (TMB) and the number of tumor neoantigens (NEO) were also measured. Results In total, 38 patients including 29 males and 9 females were recruited with a median age of 19.5 years. Among them, 12 patients had first metastases to bone (group B). The metastatic sites included femur, fibula, pelvis, ribs, sacrum, and spine. The median age of group B was 19.5 years. Twenty-six (26) patients had first metastases to lung (group L). The median age of group L was 14 years.The most frequently mutated genes in OS was TP53 (55.3%), followed by MYC (36.8%), MUC16 (26.3%), PTK2 (21.1%), RAD21 (21.1%), and CDK4 (18.4%). However, genetic features between Groups B and Group L patients were different. In group B patients, the median percentage of SNVs and short INDELs was 94.7% of the overall mutations, and the median percentage of CNVs was 4.3%. In contrast, the median percentage of SNVs and short INDELs in group L was 58.8%, and the median percentage of CNVs was 36.7%. The mutations patterns were clearly different between Group B and Group L with a predominant SNV & INDEL in Group B and a mixture feature of SNV & INDEL and CNV in Group L. Inaddition the median TMB in group B was significantly higher than that in group L (4.85 muts/Mb vs 2.4 muts/Mb, P<0.05). Also, the median number of tumor NEO in group B was nearly 6 times higher than that in group L (743 vs 128.5, P=0.0016). Conclusion Our study identified different molecular features of patients with OS firstly metastasizing to lung and to bone. OS with first bone metastases had a predominant SNV and short INDEL, high TMB level, and high NEO counts, while OS with first lung metastasis had an increased CNV, low TMB, and low NEO counts. Our results suggest that metastatic OS that firstly spread to bone and to lung may be two distinct subgroups and may adopt different treatment strategies. Citation Format: Lu Xie, Zhenyu Cai, Xiaodong Tang, Wei Guo, Fanfei Meng, Xin Zhang, Xiaoliang Shi, Fei Pang. Distinct genetic features between osteosarcomas firstly metastasizing to bone and to lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5669.

Heparan sulfate dependent binding of plasmatic von Willebrand factor to blood circulating melanoma cells attenuates metastasis

Heparan sulfate (HS), a highly negatively charged glycosaminoglycan, is ubiquitously present in all tissues and also exposed on the surface of mammalian cells. A plethora of molecules such as growth factors, cytokines or coagulation factors bear HS binding sites. Accordingly, HS controls the communication of cells with their environment and therefore numerous physiological and pathophysiological processes such as cell adhesion, migration, and cancer cell metastasis. In the present work, we found that HS exposed by blood circulating melanoma cells recruited considerable amounts of plasmatic von Willebrand factor (vWF) to the cellular surface. Analyses assisted by super-resolution microscopy indicated that HS and vWF formed a tight molecular complex. Enzymatic removal of HS or genetic engineering of the HS biosynthesis showed that a reduced length of the HS chains or complete lack of HS was associated with significantly reduced vWF encapsulation. In microfluidic experiments, mimicking a tumor-activated vascular system, we found that vWF-HS complexes prevented vascular adhesion. In line with this, single molecular force spectroscopy suggested that the vWF-HS complex promoted the repulsion of circulating cancer cells from the blood vessel wall to counteract metastasis. Experiments in wild type and vWF knockout mice confirmed that the HS-vWF complex at the melanoma cell surface attenuated hematogenous metastasis, whereas melanoma cells lacking HS evade the anti-metastatic recognition by vWF. Analysis of tissue samples obtained from melanoma patients validated that metastatic melanoma cells produce less HS. Transcriptome data further suggest that attenuated expression of HS-related genes correlate with metastases and reduced patients’ survival. In conclusion, we showed that HS-mediated binding of plasmatic vWF to the cellular surface can reduce the hematogenous spread of melanoma. Cancer cells with low HS levels evade vWF recognition and are thus prone to form metastases. Therefore, therapeutic expansion of the cancer cell exposed HS may prevent tumor progression.

Efficacy of endovascular superselective chemoembolization with HepaSphere 50–100 μm microspheres saturated with cytostatic in stopping nosebleeds in patients with nasopharyngeal cancer

The OBJECTIVE was to show the effectiveness of a new method for stopping nosebleeds in patients with nasopharyngeal cancer using endovascular superselective chemoembolization of the tumor arterial bed with HepaSphere 50–100 μm microspheres saturated with the cytostatic doxorubicin.METHODS AND MATERIALS. The results of treatment of 94 patients who against the background of progressive growth of nasopharyngeal cancer and ongoing combined treatment in oncology centers experienced nosebleeds are presented. In all these patients, according to the results of examinations in cancer centers, no convincing source of nosebleeds was identified. In the conditions of Polenov Neurosurgical Institute, 94 patients underwent endovascular superselective chemoembolization of the vasculature of nasopharyngeal cancer. The embolizate was a mixture of HepaSphere 50–100 μm microspheres saturated with the cytostatic doxorubicin (50 mg). All patients were included in the study in the absence of contraindications and after signing a voluntary informed consent approved by the ethics committee. The selection of patients was carried out according to the following criteria: thorough morphological verification of the neoplasm; locally advanced process of III and IV stages (T2-4 N0-2M0); no history of other cancers; absence of individual hematogenous metastases; absence of competitive pathology in the stage of decompensation; age was over 18 years old. All patients underwent induction-simultaneous chemoradiotherapy (CRT) with the use of radiation therapy in the usual dose fractionation regimen.RESULTS. The hemostatic effect was achieved in all 94 patients due to sequential superselective chemoembolization of the vasculature of the tumor itself with embolizate, which was a mixture of HepaSphere 50–100 μm microspheres saturated with the cytostatic doxorubicin (50mg). In the future, nosebleeds in these patients did not occur. The main sources of nosebleeds were the following branches of the external carotid artery: in 46.2 % of cases – the maxillary artery, in 37.6 % – the ascending pharyngeal artery, in 8.6 % – the occipital artery, in 5.4 % – the artery of the carotid node, in 2.2 % – other branches of the external and internal carotid arteries on one side or on both sides.CONCLUSION. The method of endovascular superselective chemoembolization with doxorubicin of the vasculature of nasopharyngeal cancer complicated by nosebleeds developed and introduced into medical practice was the initial stage of the combined treatment of these neoplasms. A good hemostatic effect was achieved in all 94 patients.

Serum Total Bile Acids in Relation to Gastrointestinal Cancer Risk: A Retrospective Study.

BackgroundBile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare.MethodsWe conducted a retrospective case–control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients’ demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models.ResultsPositive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018).ConclusionsThis retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.

Changes in dynamics of tumor/endothelial cell adhesive interactions depending on endothelial cell growth state and elastic properties.

Cancer cell adhesion to the endothelium is a crucial process in hematogenous metastasis, but how the integrity of the endothelial barrier and endothelial cell (EC) mechanical properties influence the adhesion between metastatic cancer cells and the endothelium remain unclear. In the present study, we have measured the adhesion between single cancer cells and two types of ECs at various growth states and their mechanical properties (elasticity) using atomic force microscopy single cell force spectroscopy. We demonstrated that the EC stiffness increased and adhesion with cancer cells decreased, as ECs grew from a single cell to a confluent state and developed cell-cell contacts, but this was reversed when confluent cells returned to a single state in a scratch assay. Our results suggest that the integrity of the endothelial barrier is an important factor in reducing the ability of the metastatic tumor cells to adhere to the vascular endothelium, extravasate and lodge in the vasculature of a distant organ where secondary metastatic tumors would develop.

SO-40 Measurement of circulating tumor DNA (ctDNA) in appendiceal adenocarcinoma (AA): Prevalence, predictors, and correlation with clinical outcome

Appendiceal adenocarcinoma (AA) is a rare and heterogenous cancer with marked differences in clinical course between high- and low-grade tumors. Unlike colorectal cancer (CRC) and other gastrointestinal malignancies, AA virtually never has hematogenous metastases, rather, metastasis is limited to the peritoneum. Here we present a retrospective, single institution study of AA to identify the prevalence of detectable ctDNA, evaluate the predictive value of positive ctDNA, and assess what clinical, pathologic, or molecular features predict positive ctDNA.

Клинико-морфологические особенности немелкоклеточного рака легкого у больных с разными вариантами гистологических изменений бронхиального эпителия

Lung cancer occupies the leading position in the global structure of oncological diseases. Despite significant advances in its treatment, the survival remains low. Morphological changes to the bronchial epithelium outside the tumor may provide important cues on progression of the disease in patients with lung cancer. This study aimed to identify associations between morphological and clinical features of non-small cell lung cancer and morphological changes to the epithelium in small bronchi outside the tumor. The study encompassed tumor specimens collected from 90 patients, 75 (83%) men and 15 (17%) women, diagnosed with non-small cell lung cancer. The average age of the patients was 67.8 ± 7.4 years. The results indicate higher frequency of lymphogenous metastasis in patients with combined basal cell hyperplasia and squamous metaplasia (BCH+SM+ group) compared to patients with isolated basal cell hyperplasia (BCH+SM– group, p = 0.05). The BCH+SM– group presented with higher rates of hematogenous metastasis compared to BCH+SM+ and BCH–SM– groups (p = 0.004 and p = 0.0019, respectively), as well as increased representation of low-differentiated structures in the primary tumors. The results suggest a commonality of parenchymal-stromal interactions in non-small cell lung cancers and their surroundings and a significant impact of these interactions on differentiation status and progression of the tumors.

GSDMD-dependent pyroptotic induction by a multivalent CXCR4-targeted nanotoxin blocks colorectal cancer metastases

Colorectal cancer (CRC) remains the third cause of cancer-related mortality in Western countries, metastases are the main cause of death. CRC treatment remains limited by systemic toxicity and chemotherapy resistance. Therefore, nanoparticle-mediated delivery of cytotoxic agents selectively to cancer cells represents an efficient strategy to increase the therapeutic index and overcome drug resistance. We have developed the T22-PE24-H6 therapeutic protein-only nanoparticle that incorporates the exotoxin A from Pseudomonas aeruginosa to selectively target CRC cells because of its multivalent ligand display that triggers a high selectivity interaction with the CXCR4 receptor overexpressed on the surface of CRC stem cells. We here observed a CXCR4-dependent cytotoxic effect for T22-PE24-H6, which was not mediated by apoptosis, but instead capable of inducing a time-dependent and sequential activation of pyroptotic markers in CRC cells in vitro. Next, we demonstrated that repeated doses of T22-PE24-H6 inhibit tumor growth in a subcutaneous CXCR4+ CRC model, also through pyroptotic activation. Most importantly, this nanoparticle also blocked the development of lymphatic and hematogenous metastases, in a highly aggressive CXCR4+ SW1417 orthotopic CRC model, in the absence of systemic toxicity. This targeted drug delivery approach supports for the first time the clinical relevance of inducing GSDMD-dependent pyroptosis, a cell death mechanism alternative to apoptosis, in CRC models, leading to the selective elimination of CXCR4+ cancer stem cells, which are associated with resistance, metastases and anti-apoptotic upregulation.

Immuno-morphological characteristics of bone marrow in patients with ovarian cancer

Background. Nowadays, one of the promising areas is the study of bone marrow in malignant tumors. It is known that hematogenous metastasis to the bone marrow in cancer is a common event. Identification of bone marrow lesions in ovarian cancer, as well as the study of hematopoiesis, can provide additional information about the features of metastasis of this tumor and will make it possible to assess the prospects for targeted therapy.
 Aim. To assess the possibility of detecting disseminated tumor cells in the bone marrow in patients with ovarian cancer, to establish the frequency of bone marrow damage and to analyze the relationship with the clinical and morphological parameters of the tumor.
 Materials and methods. This work includes 42 patients with ovarian cancer who received treatment at the Blokhin National Medical Research Center of Oncology. The study was carried out by morphological and immunological methods. Morphological examination of the bone marrow (counting myelograms, calculating myelogram indices, detection of tumor cells) was performed by two morphologists. Disseminated tumor cells were detected using flow cytometry (FACS Canto II, USA, Kaluza Analysis v2.1 software). Monoclonal antibodies were used: CD45, EPCAM.
 Results. Disseminated tumor cells in the bone marrow of patients with ovarian cancer were determined based on the expression of the EPCAM antigen and lack of expression of CD45 antigen. Disseminated tumor cells were found in 65.2% (n=15)of bone marrow aspirates. Disseminated tumor cells did not correlate with tumor size, lymph nodes status and stage. The frequency of bone marrow damage was higher at stage III and reached 78.6% (11 out of 14 patients), while it was 33.3% (1 of 3 patients) in stage I. 40.0% of positive cases (2 out of 5 patients) were detected at stage IV. Disseminated tumor cells were found in 78.6% (n=11) of bone marrow aspirates in primary ovarian cancer, while in recurrent ovarian cancer they were found only in 44.4% (n=4).
 Conclusion. The hematogenous dissemination of ovarian cancer in the bone marrow was established. Bone marrow lesions was noted even in the early stages of the tumor process. The frequency of detection of disseminated tumor cells in the bone marrow of patients with ovarian cancer was 65.2%. More frequent bone marrow damage was noted in primary ovarian cancer. The number of myelocytes was significantly lower in primary ovarian cancer without bone marrow damage. The number of lymphocyte was lower in cases of bone marrow lesions.

A Proposed New Clinical Classification of Metastatic Gastric Cancer: Pyloric and Antral Gastric Cancer

We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form.Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared.Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H-P-), lymphatic + hematogenous group (L+H+P-), disseminated ± lymphatic group (L±H-P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H-P- group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P- group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H-P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1).Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment.

Cathepsin G-induced malignant progression of MCF-7 cells involves suppression of PAF signaling through induced expression of PAFAH1B2

Breast cancer is primarily classified into ductal and lobular types, as well as into noninvasive and invasive cancer. Invasive cancer involves lymphatic and hematogenous metastasis. In breast cancer patients with distant metastases, a neutrophil-derived serine protease; cathepsin G (Cat G), is highly expressed in breast cancer cells. Cat G induces cell migration and multicellular aggregation of MCF-7 human breast cancer cells; however, the mechanism is not clear. Recently, platelet-activating factor (PAF)-acetylhydrolase (PAF-AH), the enzyme responsible for PAF degradation, was reported to be overexpressed in some tumor types, including pancreatic and breast cancers. In this study, we investigated whether PAF-AH is involved in Cat G-induced aggregation and migration of MCF-7 cells. We first showed that Cat G increased PAF-AH activity and elevated PAFAH1B2 expression in MCF-7 cells. The elevated expression of PAFAH1B2 was also observed in human breast cancer tissue specimens by immunohistochemical analysis. Furthermore, knockdown of PAFAH1B2 in MCF-7 cells suppressed the cell migration and aggregation induced by low concentrations, but not high concentrations, of Cat G. Carbamoyl PAF (cPAF), a nonhydrolyzable PAF analog, completely suppressed Cat G-induced migration of MCF-7 cells. In addition, PAF receptor (PAFR) inhibition induced cell migration of MCF-7 cells even in the absence of Cat G, suggesting that Cat G suppresses the activation of PAFR through enhanced PAF degradation due to elevated expression of PAFAH1B2 and thereby induces malignant phenotypes in MCF-7 cells. Our findings may lead to a novel therapeutic modality for treating breast cancer by modulating the activity of Cat G/PAF signaling.

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer.

BackgroundBiology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT.MethodsA single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake.ResultsOf this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver.ConclusionsThe majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.

Application of PET/CT in Preoperative Evaluation and Diagnosis of Gastric Cancer.

The aim study to study the significance of pet clinical examination image technology for early gastric mucosal adenocarcinoma, improve the accuracy and accuracy of image examination results of gastric cancer, and provide important reference significance and value for early treatment. Study methods, we used the experimental method of clinical medicine to obtain some reference data through the intervention of different image examinations on experimental patients of different groups and stages, These data show that the use of PET-CT imaging can improve the one-year survival rate of patients and reduce the one-year recurrence rate. Lymphatic metastasis rate and hematogenous metastasis rate, so as to highlight the advantages of PET-CT imaging.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF BONE SARCOMAS
 IN THE REPUBLIC OF KAZAKHSTAN IN 2010-2019

Relevance: Sarcomas are a heterogeneous group of malignant neoplasms (MNs) of mesenchymal origin. The peak incidence of bone tumors
 falls on a socially significant age: with osteosarcoma and Ewing’s sarcoma – 10-25 years, with chondrosarcoma – 35-40 years. Bone sarcomas
 are the most aggressive human MNs. This urges to determine the prognostic factors of the disease, timely assess the treatment effect, and identify
 possible relapses.
 The study aimed to improve the early diagnosis of bone sarcomas, to improve and increase the oncological alertness of doctors by establishing
 the trends in bone sarcoma incidence and mortality in the Republic of Kazakhstan in 2010-2019, and this disease incidence and mortality in 2019
 by age, gender, bone tumor histotype and region of the country.
 Methods: The study included the data of patients registered at the RK National Cancer Registry in 2010-2019 with a “bone sarcoma” diagnosis (ICD-10 code: C40-C41). The incidence of bone sarcomas was presented as absolute and crude rates per 100,000 population. Absolute
 standardized morbidity and mortality were calculated using the World Standard. MS Excel 2016 was used to display the results graphically.
 Results: By the end of 2019, 1587 patients were registered with bone sarcomas in the RK. From 2010 to 2019, the incidence of bone sarcoma in
 the RK decreased by 39%, including 36% among men and 40% among women. Mortality decreased by 37% to 0.8% per 100,000 population. Bone
 sarcoma is not among the 20 most common types of cancer in the RK; it accounts for 0.7% of all new cases of MN (2010-2019). The peak incidence
 of bone sarcoma was observed at the age below 20 years (20%), and mortality – in the age group of 45-54 years (22%).
 Conclusion: The rare occurrence of bone MNs can cause misdiagnosis during the initial examination. Bone sarcomas account for 0.8% of all
 MNs diagnosed in the RK; however, the aggressiveness of the course and rapid hematogenous metastasis causes a high percentage of neglect of
 this disease during the initial visit. In addition, bone sarcomas are more common than other MNs in young adults and adolescents. The prognosis
 of primary bone sarcomas depends on many factors.