Degree Of Malignancy Research Articles

Hemorrhagic complications during stereotactic biopsy of brain tumors

Relevance. Stereotactic biopsy (STB) is one of the main methods for diagnosing deep brain lesions. STB has several advantages over conventional intraoperative biopsy, as it is less traumatic and safer, especially for patients in critical condition. However, the most common complications of STB are hemorrhages, with a risk ranging from 0.9 % to 59.8 % depending on various studies. Intracranial hemorrhages are serious complications of surgical treatment of brain tumors, especially during biopsy using stereotactic techniques.Objective. To assess the risk of intracranial hemorrhages during STB of brain tumors and investigate possible factors influencing this risk, such as involvement of different brain regions in the neoplastic process, patient’s gender and age, degree of malignancy of the tumor, and use of different stereotactic devices.Materials and Methods. A retrospective study of data from 20 patients who underwent STB of brain tumors was conducted. Clinical data, examination results including coagulogram and aggregatogram, as well as data on involvement of different anatomical brain regions in the neoplastic process, degree of malignancy of the tumor, and use of a specific stereotactic device were analyzed.Results. Analysis of the frequency and structure of hemorrhagic complications of STB was performed, prognostic factors for high risk were identified, and preventive measures were proposed to reduce the number of hemorrhages.Conclusions. The introduction of the modern CRW Radionics stereotactic device into practice has reduced the frequency and severity of hemorrhagic complications after STB by two times. Lymphoproliferative processes and glioblastomas have a higher frequency of hemorrhages, but in most cases, they are clinically insignificant. There is a correlation between the degree of anaplasia of astrocytic tumors and the severity of hemorrhages. Ways to reduce the risks of intracranial hemorrhages during STB of brain tumors may include: careful preoperative planning of the biopsy trajectory; use of informative neurovisualization methods in planning the needle insertion trajectory; use of modern stereotactic systems by neurosurgeons who have undergone additional specialization and training on the specific device; use of modern biopsy needles. In addition, it is advisable to consider preoperative preventive hemostatic therapy in patients suspected of having a high degree of tumor anaplasia.

Role of tumor-associated Macrophages in Tumor Development

The role of tumor-associated macrophages (TAM) in tumor development cannot be ignored. The number of Tams is related to the malignant degree of tumors and poor prognosis. Tams with obvious heterogeneity and plasticity are the main components of solid tumor microenvironment and become a promising target for cancer immunotherapy. Targeted therapy for TAM, combined with traditional treatment methods, may bring a new dawn to the treatment of tumors. This review summarizes the origin, types, roles in tumor progression and treatment strategies of Tams, aiming to provide new ideas and methods for the research and treatment of Tams.

The diagnostic value of fluorescence in situ hybridization in secondary electroresection of bladder cancer.

To investigate the utility of fluorescence in situ hybridization (FISH) in secondary electroresection of bladder cancer. From January 2016 to April 2022, bladder cancer patients who had undergone secondary electroresection in Tongji Hospital and had preoperative urine FISH were recruited, and the positive rate, accuracy, sensitivity, specificity, genetic material changes and predictive power on malignancy degree of FISH in the secondary electroresection of bladder cancer were examined. Twenty-six patients with bladder cancer were included in this study, and 8 were confirmed by secondary electroresection, including 6 cases positive for FISH positive and 2 negative for FISH. Besides, among the subjects, 18 were without tumor recurrence, including 1 case with positive FISH results and 17 with negative FISH results. Tumor recurrence was diagnosed in 85.71% (6/7) of FISH-positive patients in secondary electroresection while only 10.53% (2/19) of FISH-negative patients were found to develop tumor recurrence in the secondary electroresection. The sensitivity of FISH for the detection of bladder cancer before secondary electroresection was 75%, with a specificity of 94.44%, and an accuracy of 88.46%. A 6-month follow-up revealed that 2 of the 8 recurrent patients underwent radical resection of bladder cancer, and the remaining 6 patients had no recurrence, as confirmed by regular bladder perfusion and microscopy. In the 18 non-recurrent patients during secondary electroresection, no recurrence developed. Urine FISH can achieve a high detection rate and specificity for secondary electroresection of bladder cancer. If a bladder cancer patient who are indicated for secondary electroresection is negative for urine FISH, the recurrence rate after secondary electroresection will be low, and the cystoscopy can be performed before deciding whether to perform secondary electroresection.

Signal-transducing adaptor protein 1 (STAP1) in microglia promotes the malignant progression of glioma.

Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays an important role in the pathogenesis of glioma. Currently, microglia (CD11b+/CD45Low) and macrophages (CD11b+/CD45High) are distinguished as distinct cell types due to their different origins. Moreover, signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies have been reported on STAP1 in GAMs. The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscopy. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mouse models. Glioma growth was monitored by bioluminescence imaging. STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting microglial phagocytosis of microglia. Increased ARG1 may be associated with the IL-6/STAT3 pathway. Impaired phagocytosis may be associated with decreased cofilin and filopodia. STAP1 is positively associated with the degree of glioma malignancy and may represent a potential novel therapeutic target for glioma.

Concordancia clínica y patológica en tumores conjuntivales: Análisis de 195 casos

PurposeThe present study aims to assess the agreement between clinical and pathological diagnosis in conjunctival tumours in a specialist ocular oncology unit. MethodsA retrospective study of consecutive patients with conjunctival tumours diagnosed at the Ocular Oncology Unit of the University Hospital of Valladolid was performed from 1992 to 2017. Tumours were classified according to their origin (epithelial, melanocytic, lymphoid, and others) and degree of malignancy (benign, premalignant, and malignant). A biopsy was performed in cases of symptomatic or growing lesions. Cohen's kappa (κ) statistics was used as an indicator of agreement between clinical and pathological diagnosis. ResultsOf 462 consecutive patients, a biopsy was required in 195 (42.2%). The agreement with the pathological diagnosis was successful in 154 (79%) cases. Analysis according to the grade of malignancy showed the lowest rate of agreement among benign (n = 83; 91.6%) and premalignant (n = 62; 90.3%) lesions, with a total agreement in malignant lesions (n = 50; 100%); the Cohen's kappa coefficient (κ) was 0.90. The highest rates of concordance were found in epithelial, melanocytic and soft tissue lesions with κ values of 1, 0.8 and 1, respectively. The worst rate of concordance was found in lymphoid lesions with a κ value of 0.3. ConclusionsMost of the conjunctival tumours were correctly identified clinically; benign and malignant lesions showed the highest rate of accuracy; however, premalignant tumours can hide micro-invasive diseases that can go unnoticed on clinical examination. The biopsy is essential for accurate diagnosis and treatment.

CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer.

Triple negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and the worst prognosis. The application of immunotherapy for TNBC is limited. This study was to verify the potential application of chimeric antigen receptor-T cells (CAR-T cells) targeting CD24 named as 24BBz in treatment of TNBC. 24BBz was constructed by lentivirus infection and then was co-culture with breast cancer cell lines to evaluate the activation, proliferation and cytotoxicity of engineered T cells. The anti-tumor activity of 24BBz was verified in the subcutaneous xenograft model of nude mice. We found that CD24 gene was significantly up-regulated in breast cancer (BRCA), especially in TNBC. 24BBz showed antigen-specific activation and dose-dependent cytotoxicity against CD24-positive BRCA tumor cells in vitro. Furthermore, 24BBz showed significant anti-tumor effect in CD24-positive TNBC xenografts and T cells infiltration in tumor tissues, while some T cells exhibited exhaustion. No pathological damage of major organs was found during the treatment. This study proved that CD24-specific CAR-T cells have potent anti-tumor activity and potential application value in treatment of TNBC.

ANALYSIS OF THE DYNAMICS OF PROSTATE CANCER DIAGNOSIS IN THE REGIONAL HOSPITAL DURING THE PERIOD 2018 – 2022

Prostate cancer is a serious medical problem around the world. In many parts of the world, prostate cancer is the leading cause of morbidity and the second leading cause of death immediately after lung cancer. The largest proportion of cases of malignant prostate tumors is in men aged 60-80 years. The Latgale region has the highest proportion of seniors in the population (22.1%). The aim of this research was to evaluate the dynamics of primary diagnostic results over 5 years period in Daugavpils hospital patients. Objects of the study are 546 patients (men) aged from 47 to 88 years who had a PSA marker and prostate biopsy results (histological responses) collected in the period from 1 January 2018 until 1 July 2022. For quantitative evaluation of histological data, the Gleason score was used, as well as its derivative GRADE (degree of malignancy). To assess the dynamics of the quality of diagnostics of prostate cancer over 5 years, the correlation coefficient between the data on the Gleason score of newly diagnosed cancer and the 5 years period of the study was used. Relationships between PSA values, Gleason scores and patient age were also assessed. The SPSS data Statistics program was used for calculation. Difficulties in diagnosis in older patients were discussed.

Increasing differential diagnosis between lipoma and liposarcoma through radiomics: a narrative review.

Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, medium, or low. The Italian Medical Oncology Association and European Society of Medical Oncology (ESMO) guidelines recommend magnetic resonance imaging (MRI) because the clinical examination is typically ineffective. The diagnosis of these rare diseases with artificial intelligence (AI) techniques presents reduced datasets and therefore less robust methods. However, the combination of AI techniques with radiomics may be a new angle in diagnosing rare diseases such as STSs. Results obtained are promising within the literature, not only for the performance but also for the explicability of the data. In fact, one can make tumor classification, site localization, and prediction of the risk of developing metastasis. Thanks to the synergy between computer scientists and radiologists, linking numerical features to radiological evidence with excellent performance could be a new step forward for the diagnosis of rare diseases.

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma

Postoperative recurrence and metastasis are the main reasons for the poor prognosis of osteosarcoma (OS). Currently, an ideal predictor for not only prognosis but also drug sensitivity and immunotherapy responses in OS patients is urgently needed. Angiogenesis plays a crucial role in tumour progression, which suggests its immense potential for predicting prognosis and responses to immunotherapy for OS. Angiogenesis patterns in OS were explored in depth in this study to construct a prognostic model called ANGscore and clarify the underlying mechanism involved in the immune microenvironment. The efficacy and robustness of the model were validated in multiple datasets, including bulk RNA-seq datasets (TARGET-OS, GSE21257), a single-cell RNA-seq dataset (GSE152048) and immunotherapy-related datasets (GSE91061, GSE173839). OS patients with a high ANGscore had a worse prognosis, accompanied by the immune desert phenotype. Pseudotime and cellular communication analyses in scRNA-seq data revealed that as the ANGscore increased, the malignant degree of cells increased, and IFN-γ signalling was involved in tumour progression and regulation of the tumour immune microenvironment. Furthermore, the ANGscore was associated with immune cell infiltration and the response rate to immunotherapy. OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies.

CHONDROSARCOMA IN THE XXI CENTURY

Chondrosarcoma (CHS) is a rare oncopathology, is the third most common primary bone tumor after multiple myeloma and osteosarcoma. It accounts for about 25 % of the total number of bone sarcomas. CHS mainly affects adults and occurs more often in people older than 40 years, in children and adolescents it is less than 5 % of all cases of primary CHS. The most common CHS sites can be any bone containing cartilage, but most often this tumor is found in pelvis, femur and shoulder bones, and ribs. CHS are divided: by origin (primary and secondary), anatomical site (central — inside the bone marrow canal, peripheral — inside the existing osteochondroma, periosteal — on the bone surface), histological degrees GI-GII-GIII. The WHO classification (2020) includes central normal, secondary peripheral, periosteal, dedifferentiated, mesenchymal and clear-cell CHS. More than 90 % of conventional CHS are tumors of low and medium malignancy degree, with a low potential for metastasis. CHS is caused by mutations in genes that control bone growth and development. The main risk factors are the patientʼs age, previous radiation, genetic factors and predisposition to oncological diseases. Diagnosis of CHS is based on a complex algorithm, which involves collecting the patient's complaints, anamnesis, clarifying clinical symptoms, imaging (X-ray, CT, MRI), histopathological picture. The biopsy conclusion is the most important in establishing the final diagnosis. However, there are several tumors whose histological picture is similar to CHS: enchondroma, chondroblastoma, osteosarcoma, giant cell tumor of bone, dedifferentiated liposarcoma, synovial sarcoma. The CHS treatment protocol is determined based on the results of anamnestic data, imaging, histopathological results, CHS classification, and its final tumor subtype. The «gold standard» remains surgical removal of the tumor. Radiation and chemotherapy don’t play a significant role in the treatment of CHS, but require further study. Targeted and immunotherapy have a certain potential, even with a high degree of CHS resistance to traditional chemotherapy.

Clinic-pathological agreement in the diagnosis of conjunctival tumours: Analysis of 195 cases

PurposeThe present study aims to assess the agreement between clinical and pathological diagnosis in conjunctival tumours in a specialist ocular oncology unit. Methodsretrospective study of consecutive patients with conjunctival tumours diagnosed at the Ocular Oncology Unit of the University Hospital of Valladolid was performed from 1992 to 2017. Tumours were classified according to their origin (epithelial, melanocytic, lymphoid and others) and degree of malignancy (benign, premalignant, malignant). A biopsy was performed in cases of symptomatic or growing lesions. Cohen´s kappa (κ) statistics was used as an indicator of agreement between clinical and pathological diagnosis. ResultsOf 462 consecutive patients, a biopsy was required in 195 (42.2%). The agreement with the pathological diagnosis was successful in 154 (79.0%) cases. Analysis according to the grade of malignancy showed the lowest rate of agreement among benign (n = 83; 91.6%) and premalignant (n = 62; 90.3%) lesions, with a total agreement in malignant lesions (n = 50; 100%); the Cohen´s kappa coefficient (κ) was 0.90. The highest rates of concordance were found in epithelial, melanocytic and soft tissue lesions with κ values of 1, 0.8 and 1 respectively. The worst rate of concordance was found in lymphoid lesions with a κ value of 0.3. ConclusionMost of the conjunctival tumours were correctly identified clinically; benign and malignant lesions showed the highest rate of accuracy; however, premalignant tumours can hide micro-invasive diseases that can go unnoticed on clinical examination. The biopsy is essential for accurate diagnosis and treatment.

Analysis of clinical characteristics and prognostic factors of elderly patients with renal cell carcinoma based on the SEER database.

To study the difference of clinical characteristics and prognostic factors from elderly patients with renal cell carcinoma (RCC), the statistical analysis was carried out based on the surveillance, epidemiology, and end results database. The relevant clinical information of 19,472 RCC patients from 2010 to 2015 were collected, and the differences of clinicopathological characteristics and survival rate was analyzed by log-rank method and Chi square test, respectively. Multivariate Cox regression model was used to explore the independent risk factors affecting the long-term survival of RCC patients. Results showed that the proportion of elderly RCC patients in the 60-64-year group in 2010 was 15.20%, but the value elevated to 18.51% in 2015, and the Chi-square test revealed the significant correlation between elderly RCC patients with gender, race, American Joint Committee on cancer stage, T stage, N stage, and M stage. The difference of survival time between the 60-69 year, 70-79 year, 80-84 year, and 85+ year group was significant, and Kaplan-Meier analysis showed a negative effects of age on survival rate of RCC patients, indicating a worsening trend with increasing age. Cox proportional hazards model analysis further confirmed that age was the important independent prognostic factor. Our study reveals that the onset age of RCC in elderly population is gradually decreasing, and the malignant degree of elderly RCC patients is increasing with age. The female elderly population could be more susceptible to RCC than male elderly population, and 85+ year population could also be cancer susceptible with a higher lymph node metastasis rate, later tumor stage, and poor prognosis, suggesting that these elderly populations should pay more attention to the RCC screening.

Anthracycline chemicals with anthracyclinone structure exert antitumor effects by inhibiting angiogenesis and lymphangiogenesis in a xenografted gastric tumor model.

It is vital to screen or develop alternative therapeutic drugs with higher curative characteristics and fewer side effects for the clinical treatment of gastric cancer. Gastric cancer cells were exposed to different auramycin G doses while determining the impact on cell viability, migration, and invasion. Then the antitumor effects of auramycin G, 5-fluorouracil (5-Fu) and their combination were evaluated. Furthermore, the molecular mechanisms of angiogenesis and lymphangiogenesis regulated by auramycin G and its analogs were investigated. Auramycin G inhibited cell viability in a dose-dependent manner, with a 50% inhibitory concentration of 23.72 ± 6.36mg/L and 32.54 ± 5.91mg/L for AGS and MGC803 cells, respectively. The migration and invasion of gastric cancer cells were significantly inhibited by 10mg/L auramycin G, which was consistent with the down-regulation of the VEGFR2-VEGFA-pPI3K-pAkt-pErk1 and VEGFR3-VEGFC-pPI3K-pAkt-pmTOR proteins. Notably, the average tumor weights were significantly reduced in both the auramycin G (2.21 ± 0.45g) of 50mg/kg body weight and auramycin G + 5-fluorouracil (5-Fu) groups (1.33 ± 0.28g), compared with the control (3.73 ± 0.56g). Considering that auramycin G decreased the growth of blood and lymphatic vessels while reducing the degree of tumor malignancy, it effectively suppressed tumors by regulating the angiogenic and lymphangiogenic pathways. The present study confirmed that auramycin G displayed a prominent antitumor activity in gastric tumor models, both in vitro and in vivo. Moreover, it was confirmed that auramycin G played a specific role in certain gastric cancer cell types, while the mechanism was validated to be associated with angiogenesis- and lymphangiogenesis-related pathway suppression.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

Integrating machine learning algorithms to systematically assess reactive oxygen species levels to aid prognosis and novel treatments for triple -negative breast cancer patients.

Breast cancer has become one of the top health concerns for women, and triple-negative breast cancer (TNBC) leads to treatment resistance and poor prognosis due to its high degree of heterogeneity and malignancy. Reactive oxygen species (ROS) have been found to play a dual role in tumors, and modulating ROS levels may provide new insights into prognosis and tumor treatment. This study attempted to establish a robust and valid ROS signature (ROSig) to aid in assessing ROS levels. The driver ROS prognostic indicators were searched based on univariate Cox regression. A well-established pipeline integrating 9 machine learning algorithms was used to generate the ROSig. Subsequently, the heterogeneity of different ROSig levels was resolved in terms of cellular communication crosstalk, biological pathways, immune microenvironment, genomic variation, and response to chemotherapy and immunotherapy. In addition, the effect of the core ROS regulator HSF1 on TNBC cell proliferation was detected by cell counting kit-8 and transwell assays. A total of 24 prognostic ROS indicators were detected. A combination of the Coxboost+ Survival Support Vector Machine (survival-SVM) algorithm was chosen to generate ROSig. ROSig proved to be the superior risk predictor for TNBC. Cellular assays show that knockdown of HSF1 can reduce the proliferation and invasion of TNBC cells. The individual risk stratification based on ROSig showed good predictive accuracy. High ROSig was identified to be associated with higher cell replication activity, stronger tumor heterogeneity, and an immunosuppressive microenvironment. In contrast, low ROSig indicated a more abundant cellular matrix and more active immune signaling. Low ROSig has a higher tumor mutation load and copy number load. Finally, we found that low ROSig patients were more sensitive to doxorubicin and immunotherapy. In this study, we developed a robust and effective ROSig model that can be used as a reliable indicator for prognosis and treatment decisions in TNBC patients. This ROSig also allows a simple assessment of TNBC heterogeneity in terms of biological function, immune microenvironment, and genomic variation.

High-risk human papillomavirus prevalence among patients with cervical cancer at Moewardi General Hospital in Surakarta, Indonesia

Link of Video Abstract: https://www.youtube.com/watch?v=Ryf_-hvseVc Introduction: In Indonesia, cervical cancer is the second most prevalent type of cancer among the general population. Cervical cancer has the second-highest mortality rate of all cancers. Infection with the Human Papilloma Virus (HPV) is one of the causes that starts the growing phase of cervical cancer. The purpose of this study, therefore, is to determine the prevalence of HPV infection in patients with cervical cancer who were examined at Dr. Moewardi Hospital and lived in the ex-Surakarta Residency. Methods: Cervical tissue biopsy at the Anatomical Pathology Installation of Dr. Moewardi General Hospital Surakarta which had been diagnosed as cervical cancer was examined by the detection of E6 protein from HPV 16 and HPV 18 using immunohistochemical staining techniques. The data obtained would be analyzed based on the characteristics of the patient's age and the degree of histopathological malignancy with a p-value &lt; 0.05 deemed significant. Results: Overall, the prevalence of high-risk HPV infection was 77.8% (35/45), with women aged between 41-55 years having the highest prevalence of HPV infection (45.7, 16/35), followed by women aged 56-70 (42.9%), women over 70 (8.6%) and women under 40 (2.9%). The results of statistical tests showed that no significant relationship was found between HPV infection and age (p = 0.428). High-risk HPV infection was most prevalent in the poorly differentiated group (54.3%), followed by the well-differentiated group (34.3%) and the moderately differentiated group (11.4%). The results of statistical tests revealed a significant association between HPV infection and tumor grade (p = 0.027). Conclusion: To lower patient morbidity and mortality, it is crucial to receive a prophylactic HPV vaccine due to the incidence of HPV 16 and 18 infections in patients with cervical cancer at the Regional Hospital Dr. Moewardi Surakarta, with a prevalence of 77.8%.

Prognostic and immunological role of Asporin across cancers and exploration in bladder cancer

BackgroundAsporin (ASPN) has been identified as a player in tumorigenesis, but its precise roles and modulatory function are largely unknown. Methods: In the present study, ASPN expression was first explored, followed by a prognostic evaluation of ASPN and a comprehensive investigation of the connections between ASPN and immunomodulation, immune cell infiltration and potential compounds on a pancancer level. Finally, ASPN expression was validated in bladder urothelial carcinoma (BLCA) tissues, and the potential function of ASPN, including its effects on migration and invasion capabilities, was investigated in tumor cells. Results: The expression of ASPN exhibited significant variation across cancers and was found to be associated with patient prognosis. In addition, the expression level of APSN was markedly correlated with the abundances of infiltrating immune cells and cancer-associated fibroblasts and the expression levels of immunomodulatory genes based on the results of pancancer analysis. Metastasis and immune-associated signaling pathways were identified in enrichment analysis based on ASPN expression. Finally, we confirmed that ASPN expression increased with the degree of malignancy in BLCA tissues and cell lines and that low expression of ASPN hindered the migration and invasion of cells. Conclusions: ASPN has the potential to be a biomarker of cancer prognosis and a therapeutic target, and it also has predictive capability for the progression of BLCA.

Bruceine D suppresses CAF-promoted TNBC metastasis under TNF-α stimulation by inhibiting Notch1-Jagged1/NF-κB(p65) signaling

BackgroundTriple-negative breast cancer (TNBC) has a poor prognosis because of its high degree of malignancy and the lack of effective treatment options. Cancer-associated fibroblasts (CAFs) comprise the most abundant stromal cells in the tumor microenvironment (TME), leading to functional impairments and facilitating tumor metastasis. Excessive TNF-α further promotes cross-talk between different cells in TME. Therefore, there is an urgent need to develop more effective therapies and potential drugs that target the key factors that promote TNBC metastasis. PurposeThe study aimed to evaluate the efficacy of Bruceine D, an active compound derived from the Chinese herb Brucea javanica, in inhibiting metastasis and elucidate the underlying mechanism of action in TNBC. MethodsIn vitro, the clonogenic and the Transwell assays were used to assess the effects of Bruceine D on the proliferation, migration and invasion abilities of co-cultured CAFs and MDA-MB-231 (4T1) cells under TNF-α stimulation. TNF-α, IL-6, CXCL12, TGF-β1, and MMP9 levels in the supernatant of co-cultured cells were determined using ELISA. Western blotting was utilized to detect the expression levels of proteins related to the Notch1-Jagged1/NF-κB(p65) pathway. In vivo, the anti-tumor growth and anti-metastatic effectiveness of Bruceine D was evaluated by determining tumor weight, number of metastatic lesions, and pathological changes in the tumor and lung/liver tissues. The inhibitory effect of Bruceine D on α-SMA+ CAFs activation and CAF-medicated extracellular matrix remodeling was accessed using immunohistochemistry, immunofluorescence, and Masson and Sirius Red staining. The expression levels of Notch1, Jagged1 and p-NF-κB(p65) proteins in the primary tumors were measured by immunohistochemistry and western blotting. ResultsIn vitro, Bruceine D significantly inhibited the migration and invasion of co-cultured CAFs and MDA-MB-231 (4T1) cells under TNF-α stimulation, reduced the expression of tumor-promoting and matrix-remodeling cytokines secreted by CAFs, and hindered the mutual activation of Notch1-Jagged1 and NF-κB(p65). In vivo, Bruceine D significantly suppressed tumor growth and the formation of lung and liver metastases by decreasing TNF-α stimulated α-SMA+ CAFs activation, collagen fibers, MMPs production, and inhibited Notch1-Jagged1/NF-κB(p65) signaling in TNBC-bearing mice. ConclusionBruceine D effectively weakened the "tumor-CAF-inflammation" network by inhibiting the mutual activation of Notch1-Jagged1 and NF-κB(p65) and thereby suppressed TNBC metastasis. This study first explored that Bruceine D disrupted the cross-talk between CAFs and tumor cells under TNF-α stimulation to inhibit the metastasis of TNBC, and highlighted the potential of Bruceine D as therapeutic agent for suppressing tumor metastasis.

Multifunctional Nanoprobe Based on Fluorescence Resonance Energy Transfer for Furin Detection and Drug Delivery.

Triple-negative breast cancer is particularly difficult to treat because of its high degree of malignancy and poor prognosis. A fluorescence resonance energy transfer (FRET) nanoplatform plays a very important role in disease diagnosis and treatment due to its unique detection performance. Combining the properties of agglomeration-induced emission fluorophore and FRET pair, a FRET nanoprobe (HMSN/DOX/RVRR/PAMAM/TPE) induced by specific cleavage was designed. First, hollow mesoporous silica nanoparticles (HMSNs) were used as drug carriers to load doxorubicin (DOX). HMSN nanopores were coated with the RVRR peptide. Then, polyamylamine/phenylethane (PAMAM/TPE) was combined in the outermost layer. When Furin cut off the RVRR peptide, DOX was released and adhered to PAMAM/TPE. Finally, the TPE/DOX FRET pair was constituted. The overexpression of Furin in the triple-negative breast cancer cell line (MDA-MB-468 cell) can be quantitatively detected by FRET signal generation, so as to monitor cell physiology. In conclusion, the HMSN/DOX/RVRR/PAMAM/TPE nanoprobes were designed to provide a new idea for the quantitative detection of Furin and drug delivery, which is conducive to the early diagnosis and treatment of triple-negative breast cancer.

What factors are associated with the prognosis of primary testicular diffuse large B-cell lymphoma? A study based on the SEER database.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a relatively rare urological tumor with a high degree of malignancy and a poor prognosis. This study aimed to investigate the prognostic risk factors for survival of patients with PT-DLBCL, and then to construct a predictive model and verify its reliability. First, we selected subjects from the SEER database (2000-2018) and analyzed the survival of PT-DLBCL patients by Kaplan-Meier test. Then, we analyzed prognostic factors by Cox regression. Finally, the data from the training cohort were used to construct a prediction model and represented with a nomogram. We evaluated the nomogram using the consistency index (C-index), decision curve analysis (DCA), and the area under the subject operating characteristic curve (ROC). In addition, calibration curves were plotted to assess the agreement between the column plot model and the actual model. We identified five independent risk factors for patient prognosis affecting OS and CSS in patients with PT-DLBCL by univariate and multivariate analysis, including age, transversality, Ann Arbor staging, chemotherapy, and radiotherapy. According to the above factors, we constructed prognostic nomograms, and found that age contributed the most to the survival of patients with PT-DLBCL. The C-indexes for the nomogram of OS and CSS in the training cohort were 0.758 (0.716-0.799) and 0.763 (0.714-0.812), and in the validation cohort were OS and CSS 0.756 (0.697-0.815) and 0.748 (0.679-0.817). We produced the first nomogram of PT-DLBCL, and it can be used to evaluate the CSS and OS of patients to determine the prognosis of patients.