Neoplastic Invasion Research Articles

Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.

Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.

Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

Comparative Study between Vascularized Flap and Free Graft in CSF Rhinorrhoea (success rate): Meta-Analysis Study

Abstract Background CSF rhinorrhea refers to CSF leakage into the nasal cavity. Most commonly, CSF enters the nasal cavity through defects in the anterior skull base. CSF leak is a serious condition occurring spontaneously or as a result of increased ICP, head trauma, surgery, neoplastic invasion, inflammatory erosion of the skull base, or congenital malformations. Objective Our meta-analysis study is to compare between free grafts and prdicled nasal flaps in repairing CSF rhinorrhea regarding success rate, complications, operative time and hospital stay. Methodology The total number of patients in all the included studies was 524 patients; 339 in the free graft group and 185 in the vascularized flap group. Results Our meta-analysis study showed that success rate in free graft group was 88.5%, while, in vascularized flap group was 93% and the complications rate in free graft group was 39%, while, in vascularized flap group was 39.3%. The result of our meta-analysis showed no significant difference between free grafts and vascularized nasal flaps in reconstruction of skull base in CSF rhinorrhea regarding success rate and complications rate. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Conclusion We found no significant difference between free grafts and vascularized nasal flaps in reconstruction of skull base in CSF rhinorrhea regarding success rate and complications rate. Choosing between them depends on the surgeon’s experience and the location and the size of the defect.

Abstract 6959: Acetylcholine potentiates invasion and migration of human pancreatic cancer cells under hypoxia through α7 nAChR-mediated increases in HIF-1α expression

Abstract The most significant nerve-related problem in clinical pancreatic cancer management is perineural invasion (PNI), characterized as the neoplastic invasion of cancer cells into or surrounding the nerves. It is a characteristic feature of pancreatic ductal adenocarcinoma (PDAC) associated with a poor prognosis, tumor recurrence, and emergent pain. However, why PDAC is associated with a higher incidence of PNI remains unclear. HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~1000 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying neurotransmitter acetylcholine (Ach)-potentiated HIF-1α expression and subsequent increase in invasion and migration of human pancreatic cancer cells in hypoxia (2% O2). The expression of various acetylcholine receptors in six types of pancreatic cancer cell lines (MIA-PaCa-2, PANC-1, HPAF-II, Capan-1, AsPC-1, and BxPC-3 cells) was observed using qPCR, and α7 nAChRs was observed to be expressed in all pancreatic cancer cells. Therefore, we chose MIA-PaCa-2 cells, expressing high levels of α7 nAChRs, and HPAF-II cells, expressing low levels of α7 nAChRs, for loss- and gain-of-function studies, respectively. In vitro assays showed that, under hypoxic conditions, Ach caused a concentration-dependent increase in α7 nAChRs-mediated HIF-1α expression, enhancing expression of HIF-1α target genes, and promoting invasion and migration of human pancreatic cancer cells. We further found that Ach increased HIF-1α protein stability in pancreatic cancer cells under hypoxic conditions. This effect was mediated by YAP signaling, as evidenced by the fact that Ach-induced increases in HIF-1α protein stability were blocked by siRNA-mediated knockdown of YAP. Consistent with these findings, an investigation of the relationship between α7 nAChRs and clinicopathological features in pancreatic cancer patients using publicly available datasets showed that high levels of α7 nAChRs are correlated with a poorer prognosis in pancreatic cancer patients. Collectively, these findings identify novel mechanisms by which Ach potentiates invasion and migration of pancreatic cancer cells and provide further evidence that HIF-1α is a potential anticancer target in Ach-associated pancreatic cancer. Citation Format: Yunmi Cho, Eun-Taex Oh, Ha Gyeong Kim, Heon Joo Park. Acetylcholine potentiates invasion and migration of human pancreatic cancer cells under hypoxia through α7 nAChR-mediated increases in HIF-1α expression [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 6959.

Cyclooxygenase-2 (COX-2) Expression in Equine Melanocytic Tumors.

Equine melanocytic tumors are common and have an unusual benign behavior with low invasiveness and metastatic rates. However, tumoral mass growth is usually a concern that can have life-threatening consequences. COX-2 is related to oncogenesis, promoting neoplastic cell proliferation, invasion, and metastasis. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in equine melanocytic tumors. Through extension and intensity of labeling, 39 melanocytomas and 38 melanomas were evaluated. Of the malignant tumors, 13.2% were negative and 63.2% presented a low COX-2 expression. Only 6 malignant tumors presented >50% of labeled cells, 18 malignant and 8 benign had an expression between 21 and 50%, 8 malignant and 3 benign tumors had an expression between 6 and 20%, 1 malignant tumor had an expression between 1 and 5%, and 5 malignant and 28 benign tumors had no expression. Malignant tumors showed higher COX-2 expression than did benign tumors, with statistically significant differences. The low levels of COX-2 may be one of the molecular reasons for the presence of expansive mass growth instead of the invasive pattern of other species, which is related to high COX-2 levels.

Intramural and Adapted-Germ Cell Neoplasia In situ

Germ cell neoplasia in situ emerges as a precursor lesion configuring type II germ cell tumours as testicular seminoma or post-pubertal non-seminomatous testicular germ cell tumours. Lesion is comprised of neoplastic gonocyte-like cells, latent totipotent or naive germ cells with developmental potential situated within ‘spermatogonial niche’ of seminiferous tubules. Germ cell neoplasia in situ delineates an increased incidence with conditions as uncorrected cryptorchidism, ambiguous genitalia, infertility or preceding history of post-pubertal germ cell tumour within contralateral testis. Neoplasm demonstrates aneuploidy or polypoid genotype with additional chromosomal gains as is chromosome 12p upon commencement of neoplastic invasion. Neoplastic cells appear enlarged, atypical, gonocyte-like and are incorporated with abundant, clear cytoplasm, enlarged, hyper chromatic nuclei, coarse nuclear chromatin, angulated cellular margins and prominent nucleoli.

Dispne ile başvuran bir kronik obstruktif akciğer hastasında intrakardiyak kitleden tanı alan skuamoz hücreli karsinom olgusu

Primary cardiac tumor is a rare disease with an incidence ranging from 0.001% to 0.03%. Cardiac metastases are more common than primary tumors. The most frequently metastasized tumors are lung, breast, kidney cancers and melanomas. Several published case reports have documented non-small cell lung cancer (NSCLC) patients with neoplastic heart invasion. However, the number of small cell lung cancer (SCLC) cases with neoplastic cardiac invasion is limited. In this article, we present our case of non-small cell lung cancer with cardiac invasion who presented to the emergency department with dyspnea.

The possible role furin and furin inhibitors in endometrial adenocarcinoma: A narrative review.

Endometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC. Furin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro-metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro-renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation. Furin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro-renin receptor, CD109, and TGF-β. As well, EAC-mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.

Differential Perspectives Between miRNA and lncRNA in Light of Biogenesis and Functions: A Review

The central dogma is suggested that deoxyribonucleic acid is translated into ribonucleic acid (RNA) and then into protein. It is considered that 2–3% of the genomic DNA in a functionally active cell, is transcribed to protein-coding RNA. The presence of noncoding transcripts has been neglected many a time as cellular DNA and transcript noises, however, increasing proof proposes that a very important part of these non-coding transcripts is functionally effective as RNA molecules. The non-coding transcripts of up to 100 bases are known as small non-coding RNA that comprises tRNA, miRNA, snoRNA, piwi-interacting RNA (pi-RNA), etc. Interestingly, rRNA features about 6.9 kb, though these are not considered long-non-coding RNAs. However, RNA molecules that are over 200 bases long (ranging between 0.8 to 10 kb) are known as long non-coding RNA (lncRNA). It does not have open reading frames (with some exceptions), 3`- untranslated regions (3’-UTRs), and these RNAs are devoid of any translation-termination regions. However, these may be capped, spliced, and polyadenylated as RNA molecules and play a major role in factor regulation, neoplastic cell invasion, chromatin granule transforming, and cell differentiation. Downregulation of lncRNA is responsible for numerous diseases in mammals. miRNAs are mature transcripts of 22 nt in length and function as antisense regulators of other RNAs. They play role in post-transcriptional factors and are involved in differentiation, proliferation, immune response, cell growth, and caspase-mediated cell death. Downregulation in miRNA expression has a necessary role in many diseases, together with cancers.

Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma.

Mounting evidence links the phenomenon of enhanced recruitment of tumor-associated macrophages towards cancer bulks to neoplastic growth, invasion, metastasis, immune escape, matrix remodeling, and therapeutic resistance. In the context of cancer progression, naïve macrophages are polarized into M1 or M2 subtypes according to their differentiation status, gene signatures, and functional roles. While the former render proinflammatory and anticancer effects, the latter subpopulation elicits an opposite impact on pancreatic ductal adenocarcinoma. M2 macrophages have gained increasing attention as they are largely responsible for molding an immune-suppressive landscape. Through positive feedback circuits involving a paracrine manner, M2 macrophages can be amplified by and synergized with neighboring neoplastic cells, fibroblasts, endothelial cells, and non-cell autonomous constituents in the microenvironmental niche to promote an advanced disease state. This review delineates the molecular cues expanding M2 populations that subsequently convey notorious clinical outcomes. Future therapeutic regimens shall comprise protocols attempting to abolish environmental niches favoring M2 polarization; weaken cancer growth typically assisted by M2; promote the recruitment of tumoricidal CD8+ T lymphocytes and dendritic cells; and boost susceptibility towards gemcitabine as well as other chemotherapeutic agents.

(368) Stuttering Priapism: A Rare Manifestation of Underlying Malignancy

Abstract Introduction First described by Peacock in 1938, malignant priapism (MP) is defined as persistent erection in the absence of sexual stimulation or other triggering factors. The proposed mechanism is due to neoplastic invasion of cavernous sinuses and venous system resulting in poor outflow and painful penile engorgement. Though rare, MP due to penile tumors has been described in cases of hematologic malignancies, primary penile neoplasms, local invasion from urologic primary tumors including prostate and bladder cancer, and penile metastasis from other primary sources. Objective Here we describe a case of metastatic epithelioid sarcoma that presented with recurrent priapism. Methods An otherwise healthy 43 year old male presented with two weeks of intermittent priapism. Initially thought to be traumatic in nature, the patient was managed conservatively with penile irrigation and phenylephrine. Though the patient achieved some improvement in his pain, full detumescence was never achieved. Approximately one month later the patient elected for placement of an inflatable penile prosthesis (IPP) due to persistent incomplete detumescence. At the time of surgery, extensive corporal induration was noted bilaterally. Upon entry into the corpora, copious purulent material was expressed from the tissues and the decision was made to abort the case. Prior to closure, several representative biopsies were collected. Results Blood gas performed at initial presentation was consistent with low flow priapism. Doppler studies showed intact arterial blood flow to the penis bilaterally and pelvic MRI was negative for penile injury though asymmetric enhancement of the corpora was noted incidentally. Surgical pathology revealed an unclassified malignancy and increased proliferation concerning for metastasis. A PET scan was performed which was consistent with widely metastatic disease with mets to the liver, lung, bone, muscles, adrenal glands, brain, and penis. Percutaneous biopsy of an abdominal mass confirmed the diagnosis of epithelioid sarcoma. Despite palliative chemotherapy and radiation the patient succumbed to his cancer just two months after diagnosis. Conclusions Epithelioid sarcoma is a rare soft tissue neoplasm primarily affecting young adult males and representing less than 1% of soft tissue sarcomas. Even rarer is the incidence of metastatic penile tumors, with fewer than 500 cases reported in the literature since 1850. A literature review by Lin YH et al based on reports from 2006 to 2011 suggested that the true incidence of penile metastasis may be higher given that 12% of penile metastasis may be asymptomatic and discovered only at autopsy. To our knowledge, this is the first case of widely metastatic epithelioid sarcoma presenting with priapism secondary to penile metastasis. Disclosure No

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Effect of Percutaneous Biliary Drainage on Enzyme Activity of Serum Matrix Metalloproteinase-9 in Patients with Malignant Hilar Obstructive Hyperbilirubinemia.

Background and Objectives. Cholestasis activates complex mechanisms of liver injury and as a result has an increased production of matrix metalloproteinases (MMP). Depending on the stage of liver disease, different matrix metalloproteinases expressions have been detected and could serve as indirect biomarkers as well as therapeutic targets. MMP-9 proteolytic activity has a proven role in both liver regeneration and neoplastic cell invasion in various malignancies. The purpose of this prospective cohort study was to evaluate the effect of external biliary drainage on enzyme activity of MMP-9 in the serum of patients with malignant hilar biliary obstruction. Materials and Methods. Between November 2020 and April 2021, 45 patients with malignant hilar biliary obstruction underwent percutaneous biliary drainage following determination of serum MMP-9 enzyme activity (before treatment and 4 weeks after the treatment) by gelatin zymography. Results. MMP-9 values decreased statistically significantly 4 weeks after percutaneous biliary drainage (p = 0.028) as well as the value of total bilirubin (p < 0.001), values of direct bilirubin (p < 0.001), aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p < 0.001), and gamma-glutamyl transferase (GGT) (p < 0.001). Conclusions. In patients with malignant hilar biliary obstruction treated by external percutaneous biliary drainage for cholestasis resolution, a significant reduction in MMP-9 serum values was noted 4 weeks after the treatment.

Urinary Bladder Masses, Rare Subtypes, and Masslike Lesions: Radiologic-Pathologic Correlation

Urinary bladder masses are commonly encountered in clinical practice, with 95% arising from the epithelial layer and rarer tumors arising from the lamina propria, muscularis propria, serosa, and adventitia. The extent of neoplastic invasion into these bladder layers is assessed with multimodality imaging, and the MRI-based Vesical Imaging Reporting and Data System is increasingly used to aid tumor staging. Given the multiple layers and cell lineages, a diverse array of pathologic entities can arise from the urinary bladder, and distinguishing among benign, malignant, and nonneoplastic entities is not reliably feasible in most cases. Pathologic assessment remains the standard of care for classification of bladder masses. Although urothelial carcinoma accounts for most urinary bladder malignancies in the United States, several histopathologic entities exist, including squamous cell carcinoma, adenocarcinoma, melanoma, and neuroendocrine tumors. Furthermore, there are variant histopathologic subtypes of urothelial carcinoma (eg, the plasmacytoid variant), which are often aggressive. Atypical benign bladder masses are diverse and can have inflammatory or iatrogenic causes and mimic malignancy. © RSNA, 2022 Online supplemental material is available for this article.

411 AN UNEXPECTED (AND UNDESIRED) ECHOCARDIOGRAPHIC FINDING IN A PATIENT WITH RIGHT-SIDED CHEST PAIN

Abstract A 71-year-old man, former smoker, without other cardiovascular risk factors nor previously known cardiological history, was admitted to our emergency department for nonproductive cough and right-sided chest pain, worsened by inspiration. ECG documented reduced peripheral QRS voltages. Echocardiography was performed, revealing the presence of an inhomogeneous, hyperechoic neoformation involving the lateral wall of the right ventricle (RV), dislocating the right coronary artery, protruding into the cavity towards the intraventricular septum and reaching the sub-valvular apparatus of the tricuspid valve, without any hemodynamic interference. Pericardial effusion was also documented (maximum 20 mm around the atrioventricular groove), without signs of cardiac tamponade. For better mass characterization, a computed tomography (CT) scan and a cardiac magnetic resonance (CMR) were performed, confirming the presence of a solid neoformation involving the RV and pericardial effusion, also showing right pleural effusion. Furthermore, right hilar and subcarinal lymphadenomegaly with compression of the bronchi was observed. A positron emission tomography (PET) scan showed areas of increased 18-fluorodeoxyglucose (18FDG) uptake in supra- and infra diaphragmatic lymph nodes, adrenal glands, bones, and lungs. Due to the clinical suspicion of a lymphoproliferative neoplasm, corticosteroid therapy was started. Before a diagnostic lymph node biopsy could be performed, the patient had a syncopal episode due to cardiac tamponade, requiring pericardiocentesis. During hospitalization, continuous heart monitoring revealed intermittent third-degree atrioventricular block, so a permanent pacemaker was implanted. Finally, an excisional lymph node biopsy was obtained, and a diagnosis of diffuse large B-cell lymphoma was established. Treatment with Prednisone, Cyclophosphamide, Vincristine, nonpegylated liposomal Doxorubicin, and Rituximab (R-COMP) was promptly started. Seven months later, after five cycles of chemotherapy, complete remission was documented by PET scan, and the cardiac mass was no longer evident at echocardiography. Metastatic involvement of the heart is a relatively frequent event in oncologic patients, with an estimated prevalence of 8% at autopsy. Lymphoproliferive neoplasms have a not negligible rate of heart mestastatization (9,4%). Neoplastic invasion secondary to lymphoma tends to infiltrate the myocardium, typically causing arrhythmias and conduction disturbances. Diagnostic evaluation relies upon echocardiography, CT and CMR. PET/TC is of paramount importance to assess the malignant nature of the mass, to stage the disease and to evaluate the response to chemotherapy. Metastatic cardiac involvement typically occurs as a late manifestation of disseminated lymphoma and the prognosis is usually poor; however, survival is increasing thanks to new chemo-immunotherapy strategies.

Neoplastic bone marrow invasion:rapid exclusion of hematological disease by flow cytometric routine panels

Multiparametric flow cytometry is an extensively used technique to assess the presence of different cellular populations in immunology and hematology. During routine immunophenotyping analysis, it is not uncommon to face cells of non-hemopoietic origin, negative for CD45 and other myeloid, megakaryocytic, B and T lineage antigens and positive for at least one antibody among CD56, CD117 and CD138. If cytology cannot identify cell origin, especially in cases of unclear interpretation, the contribution of multiparametric flow cytometry analysis can be crucial. We report 6 patients with a clinical suspicion of hematological disease in which multiparametric flow cytometry was extremely useful to quickly exclude blood disorders in order to initiate patients to the most appropriate diagnostic process.

Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights

BackgroundSquamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED).Materials and methodsBiopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1.ResultsAC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma.ConclusionLaminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.

Cranial Spinal Spreading of Canine Brain Gliomas after Hypofractionated Volumetric-Modulated Arc Radiotherapy and Concomitant Temozolomide Chemotherapy: A Four-Case Report.

Simple SummaryGliomas represent the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone and the prognosis is generally inauspicious. In this work, a more aggressive radiotherapy protocol with concomitant radiosensitizing chemotherapy is represented but spinal-spread of the disease is reported, despite the fact that it was originally located exclusively in the brain area. This work suggests that the entire central nervous system should be investigated in diagnostic examinations and during the follow-up of canine gliomas. A radiotherapy dose-escalation trial and different chemotherapy dosages on a larger number of animals could estimate the optimal protocol to avoid spinal-spread while limiting radio-chemo toxicities. In the same context, prophylactic treatment to the spinal cord with a lower dose could also be the key to preventing recurrence across the cranial–spinal pathway and to improving quality of life.Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial–spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

A multi-task deep learning framework for perineural invasion recognition in gastric cancer whole slide images

Perineural invasion (PNI) is the process of neoplastic invasion of the nerves and is a prognostic factor in gastric cancer. However, such examination is a labor-intensive task in high-resolution digital pathological images. To alleviate this problem, we propose a multi-task deep learning-based framework to highlight diagnostically significant PNI regions in whole slide images (WSIs) of human gastric cancer tissue sections. The proposed framework includes a gastric cancer segmentation model, neural detection model, and PNI decision-making module, which realizes the segmentation of the gastric cancer region while completing the task of identifying PNI. Adequate comparative experiments were performed on our own gastric cancer PNI dataset called GC-PNI. Experiments have shown that our proposed model can effectively diagnose PNI with a high sensitivity of 0.972 and a specificity of 0.933, illustrating the potential of this practical application.

In Vitro and In Vivo Assays Characterizing MAO A Function in Cancers.

Emerging studies, including ours, have revealed the novel essential roles of monoamine oxidase A (MAO A) in mediating the growth and progression of several types of cancers. Recently, we presented the first evidence of MAO A's ability to promote cancer cell perineural invasion, the neoplastic invasion of nerves widely recognized as a significant route for cancer metastasis. Here, we describe a perineural invasion in vitro assay using a 3D coculture with a cancer cell line and an immortalized dorsal root ganglion neuronal cell line for rapid examination of MAO A's roles in cancer-nerve cell crosstalk and evaluating the efficacy of MAO A inhibitors for disrupting perineural invasion. We also summarized the fundamental methods for determining MAO A's effects on cancer cell proliferation in vitro and tumorigenesis in vivo.