Incidence Of Tumors Research Articles

Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth

Metastasis is a leading cause of mortality in breast cancer, as metastatic disease is often aggressive and resistant to conventional treatments. Cancer cells that spread to distant organs can enter a dormant phase for extended periods, sometimes years or decades. During this dormant phase, cancer cells avoid immune and pharmacological response. Thus, new approaches are needed to prevent these disseminated cells from becoming lethal cancers. Statins are known inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that have been extensively used in patients with cardiovascular diseases to lower cholesterol. However, recent research has demonstrated their potential in anticancer therapies. Epidemiological evidence suggests that statins are associated with a reduction in breast cancer-specific mortality, although they do not appear to affect the incidence of primary tumors. In this review, we discuss the role of statins in metastasis and dormancy, their cytocidal and cytostatic effects and their interactions with different cell types in the tumor microenvironment. The exact mechanisms by which statins reduce mortality without influencing primary tumor growth remain unclear, also warranting further investigation into their potential role in metastasis and tumor dormancy, which could ultimately help patients to improve survival and quality of life.

Squamous Cell Carcinoma in Upper Aerodigestive Tract: Comparative Study In between Smoking Tobacco and Smokeless Tobacco Products

Background: Squamous cell carcinoma in upper aerodigestive tract is most often caused by smoking. Smokers get laryngeal cancer, while chewers get mouth cancer. With the surge in smokeless tobacco use, it's important to determine if this differentiation influences clinical and pathological characteristics beyond site distribution. Objective: The purpose of the present study was to assess any relation between tobacco smoking, oral intake of tobacco with betel leaf or tobacco powder and squamous cell carcinoma in upper aero digestive tract. Methodology: This cross-sectional study was conducted in a single Diagnostic center at Dhaka, Bangladesh for a period of one year from July 2022 to June 2023 on patients presented with histopathologically established upper aerodigestive tract malignancies. Patients age, gender and involved site was taken from the patients report. Results: Male were predominant than female. Male to female ratio was 3.3:1. Mean age of the patients was 59.26 ± 12.55 years of the male and 56.11 ± 13.13 years of the female. Cancer was more in female at 5th and 6th decade whereas cancer was found more in male at 6th and 7th decade. Most common location of the lesions was sub-glottis (27.6%) and tongue (20.0%). The most common causes of Upper Aerodigestive Tract cancer were smoking (76.2%) and smokeless tobacco using (54.1%). There was no association between smoke and smokeless tobacco with severity of carcinoma. Maximum cases of carcinoma were grade II but there was no significant difference in grade of carcinoma between tobacco smoker and tobacco non-smoker. There was no significant difference in grade of malignancy between tobacco user and non-user. Conclusion: Smoke and/or smokeless tobacco user have increased risk of development squamous cell carcinoma in upper aerodigestive tract. However, there is no significant difference between incidence and grade of tumor among only smoker, smokeless tobacco user or both. Journal of National Institute of Neurosciences Bangladesh, January 2024;10(1):52-56

Prevalence of extracolonic malignancies in patients with familial adenomatous polyposis.

103 Background: Familial adenomatous polyposis (FAP) is an autosomal-dominant inherited colorectal cancer syndrome resulting from mutations in the adenomatous polyposis coli ( APC ) gene. Patients with FAP have nearly 100% lifetime risk of colorectal cancer, typically managed with prophylactic colectomies. As patient survival has improved, the incidence of extracolonic tumors, including thyroid malignancies and desmoid tumors, has increased. However, limited research exists on the prevalence of extracolonic malignancies in FAP patients. Methods: We prospectively enrolled 219 patients with FAP in the Hereditary Gastrointestinal Cancers Cohort at the MD Anderson Cancer Center between December 2015 and July 2024. Inclusion criteria included either a clinical or molecular diagnosis of FAP. Data on demographics, cancer history (including cancers diagnosed both prior to and during the study period), BMI, tobacco use, medications, endoscopy results, thyroid ultrasound findings, and abdominal/pelvic CT results were collected. Screening for thyroid and desmoid tumors was provider-dependent, with additional screenings as deemed appropriate. Descriptive and inferential statistics were used to identify associations between demographic and clinical factors and the prevalence of extracolonic malignancies. Results: Among 219 patients, 20.5% developed desmoid tumors, 18.7% developed colorectal cancer, and 6.8% developed well-differentiated thyroid cancer (6.4% papillary thyroid cancer, 0.4% follicular thyroid cancer). Prophylactic colorectal surgery was performed in 151 patients (68.9%). Per chart review, benign thyroid disease and hypothyroidism were present in 21% and 11.4% of patients, respectively. Female sex was significantly associated with hypothyroidism (p=0.007) and thyroid cancer (p=0.009). BMI > 30 was also linked to increased thyroid cancer risk (p=0.046). Desmoid tumors were found in 20.5% of patients, most commonly in the abdominal wall. Female sex, BMI > 30, and history of colorectal surgery were significantly associated with desmoid tumor development (p=0.004, 0.0064, 0.0038). Conclusions: FAP patients exhibit a higher prevalence of benign thyroid disease, thyroid cancer, and desmoid tumors compared to the general population. Given these findings, adherence to existing surveillance guidelines, such as those outlined by the National Comprehensive Cancer Network (NCCN), is essential. Our findings further support the importance of these established surveillance strategies in the management of FAP patients.

20 Rising incidence of pott puffy tumor: a case of a pediatric disease in a healthy adult

20 Rising incidence of pott puffy tumor: a case of a pediatric disease in a healthy adult

Molecular and clinical profiling of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs): An analysis of the Oncology Research Information Exchange Network database.

669 Background: The incidence of neuroendocrine tumors (NETs) is approximately 7 per 100,000 persons and rising. By location, tumors in the gastroenteropancreatic (GEP) region, particularly midgut NETs, are most common. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling, providing opportunities to identify novel associations between molecular features and clinical outcomes in GEP-NETs. Methods: Survival analyses were performed using the log-rank testing, and clinical features were evaluated using Wilcoxon and chi-squared tests. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test. Transcriptomic analyses utilized a student’s t-test. We reviewed 240 samples from 226 patients, with 124 of pancreatic origin, 90 small bowel, 16 gastric, and 10 colorectal. All specimens were well-differentiated; further grading information was unavailable on the ORIEN platform. A p-value <0.05 was considered significant. Results: Patients with metastatic disease were significantly younger at diagnosis (58 vs. 61 years, p=0.0242) and had significantly higher tumor mutational burden (TMB) (0.48 vs. 0.32 mut/Mb, p=0.001). Among the 100 most common alterations across the entire cohort, BPTF (p=0.03) and PRKCA (p=0.007) mutations were more prevalent in pancreatic NETs than in other primary sites. The most frequently mutated genes identified included TTN (27.7%), MUC16 (25.1%), CCDC168 (22.1%), KIR3DL1 (20%), TGIF2LX (20%), MUC17 (19.1%). TTN mutation was significantly associated with higher TMB (p<0.0001). The most common copy number alteration was MUC3a amplification (7q22.1) in 61.5% of samples. This amplification was associated with more prolonged overall survival (OS) with a significance of p=0.0501. Patients with NETs harboring a mutation in CSNK2A2 (p=0.0149), WDR74 (p=0.0386), or NCMAP (p=0.0248) experienced significantly shorter OS compared to the cohort as a whole. Conclusions: We report the first clinical, genomic, and transcriptomic analysis of ORIEN GEP-NET cases. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of well-differentiated NETs. Most prevalent mutations in GEP-NETs from ORIEN database. Mutation Prevalence (Percentage of Samples) TTN 27.7% MUC16 25.1% CCDC168 22.1% KIR3DL1 20.0% TGIF2LX 20.0% MUC17 19.1%

Chemoprotective Potential of Cyanidin-3-Glucoside Against 1,2-Dimethylhydrazine-Induced Colorectal Cancer: Modulation of NF-κB and Bcl-2/Bax/Caspase Pathway.

Colorectal cancer (CRC) represents a significant global health challenge, with approximately 1.8 million new cases diagnosed annually and a mortality toll exceeding 881,000 lives each year. This study aimed to evaluate the chemoprotective efficacy of Cyanidin-3-glucoside (C3G) in a rat model of CRC induced by 1,2-dimethylhydrazine (DMH). Rats were stratified into groups and administered C3G at doses of 10 and 15 mg/kg following DMH exposure to initiate CRC. Key parameters, including organ weights, tumor burdens, and biochemical markers, were meticulously assessed. Administration of C3G significantly restored body weight while reducing the weights of colon and spleen tissues. Moreover, C3G treatment substantially suppressed tumor incidence and weight in DMH-induced CRC rats. Biochemical analysis revealed that C3G markedly reduced levels of CFA, CA19.9, LDH, and nitric oxide (NO). It also modulated lipid profiles, antioxidant activities, and the expression of both Phase I and II enzymes. Inflammatory mediators, including TNF-α, IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, and IL-17, were significantly downregulated. Notably, C3G inhibited inflammatory markers such as COX-2, PGE2, iNOS, and NF-κB while promoting Caspase-3, -6, and -9 activity. Furthermore, it regulated the Bax/Bcl-2 apoptotic axis, reducing the Bcl-2/Bax ratio. Cyanidin-3-glucoside demonstrated potent chemopreventive effects against colorectal cancer in this experimental model. Its mechanism of action is likely mediated through modulation of NF-κB and the Bcl-2/Bax/Caspase pathway, suggesting its potential as a therapeutic agent in CRC management.

Ginkgolide B increases healthspan and lifespan of female mice.

Various anti-aging interventions show promise in extending lifespan, but many are ineffective or even harmful to healthspan. Ginkgolide B (GB), derived from Ginkgo biloba, reduces aging-related morbidities such as osteoporosis, yet its effects on healthspan and longevity have not been fully understood. In this study, we found that continuous oral administration of GB to female mice beginning at 20 months of age extended median survival and median lifespan by 30% and 8.5%, respectively. GB treatment also decreased tumor incidence; enhanced muscle quality, physical performance and metabolism; and reduced systemic inflammation and senescence. Single-nucleus RNA sequencing of skeletal muscle tissue showed that GB ameliorated aging-associated changes in cell type composition, signaling pathways and intercellular communication. GB reduced aging-induced Runx1+ type 2B myonuclei through the upregulation of miR-27b-3p, which suppresses Runx1 expression. Using functional analyses, we found that Runx1 promoted senescence and cell death in muscle cells. Collectively, these findings suggest the translational potential of GB to extend healthspan and lifespan and to promote healthy aging.

Mitigation of experimental hepatocellular Carcinoma by Inonotus obliquus Mushroom extract in association with oxidative stress and inflammation signaling.

Chaga mushroom (Inonotus obliquus) has been a component of folk medicine treating several disorders mainly through its anti-inflammatory and antioxidant properties, yet its effects on liver carcinoma needed elucidation. This study investigated the effect of an aqueous extract of Inonotus obliquus (IOAE) against diethyl-nitrosamine/carbon tetrachloride (DEN/CCl4) induced HCC in mice and addressed its molecular mechanism. HCC was induced by a single intraperitoneal injection (i.p.) of DEN (1 mg/kg b.w.) followed by CCl4 (0.2 ml/kg, i.p., twice a week) after six weeks. IOAE (200 mg/kg b.w.) was administered orally after the induction of HCC. Physiological and hematological parameters and biochemical assays for oxidative stress markers were performed. Histopathological and immunohistochemistry for inflammation and apoptosis were performed. DEN/CCl4 caused a reduction in mice body weight and an increase in the liver weight which was significantly restored by IOAE administration. The tumor incidence of DEN/CCl4 (100 %) was reduced to about 25 % by IOAE supplementation. DEN/CCl4 caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase gamma-glutamyl transferase, acid phosphatase and bilirubin) and lipid profile markers that were significantly restored by IOAE administration. Oxidative stress markers (malondialdehyde, superoxide dismutase, catalase, nitric oxide, lactate dehydrogenase, and glutathione-s-transferase) were reduced by DEN/CCl4 which were significantly restored by IOAE treatment. The liver histopathology alterations caused by DEN/CCl4 were significantly ameliorated by IOAE treatment. Immunohistochemical studies suggest that AFP, caspase-3, COX-2, and iNOS were chronically overexpressed in DEN/CCl4-exposed mice which were notably attenuated by IOAE administration. Collectively IOAE was found to suppress tumor incidence by suppressing iNOS-COX-2-dependent inflammation and caspase-3 mediated apoptosis. Chaga mushroom showed remarkable anticancer effects against liver carcinoma through induction of apoptosis and suppression of inflammation.

Incidental High-Grade Sellar Solitary Fibrous Tumor Mimicking Non-Functioning Pituitary Adenoma: A Case Report and Literature Review

Incidental High-Grade Sellar Solitary Fibrous Tumor Mimicking Non-Functioning Pituitary Adenoma: A Case Report and Literature Review

A Clinicopathological Study of Surface Epithelial Tumors of the Ovary: A Retrospective Analysis at a Tertiary Care Center in Jeddah, Saudi Arabia.

Background Ovarian cancer is a prevalent gynecological cancer in women and one of the most common cancers globally. Factors such as the use of oral contraceptives, multiparity, and breastfeeding offer protection, while obesity, nulliparity, smoking, and genetic changes increase the risk. Ovarian cancer is asymptomatic in the early stages, typically becomes symptomatic in advanced stages, and can be divided into various histologic subtypes. This study aimed to determine the incidence of epithelial ovarian tumors according to their type and clinical presentation. Aim The study was conducted to determine the incidence of epithelial ovarian tumors according to their type and clinical presentation among women in a tertiary care center in Jeddah, Saudi Arabia. This is important becausevery few studies have been conducted in Saudi Arabia regarding the incidence of surface epithelial ovarian tumors. Methodology This retrospective cohort study utilized histopathological analysis to categorize ovarian neoplasms. Data on sociodemographic characteristics, histopathological findings, and clinical features were collected and analyzed from the tertiary care center to understand the distribution of surface epithelial ovarian tumors. The data were cleaned in Microsoft Excel (Microsoft Corp., Redmond, US) and analyzed using IBM SPSS Statistics version 29.0.0 (IBM Corp., Armonk, US). Results Our comprehensive study examined 252 women with ovarian tumors, revealing a predominant age group of 41-50 years (n=63, 25.0%), with the majority being married (n=193, 76.6%). Benign tumors were the most common (n=139, 55.2%), followed by malignant (n=87, 34.5%) and borderline (n=25, 9.9 %) tumors. The initial symptoms frequently included abdominal pain (n=105, 41.7%) and abdominal masses (n=65, 25.8%). Most tumors were primary (n=110, 43.7%). Protective factors such as breastfeeding/parity were significant (n=99, 39.3%), while nulliparity was a notable risk factor (n=31, 12.3%). The most elevated tumor marker was cancer antigen 125 (CA-125) (n=93, 36.9%). Treatment often involved total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) (n=92, 36.5%), with some requiring additional chemotherapy (n=36, 14.3%). Conclusion Our study demonstrated that surface epithelial tumors, particularly serous epithelial tumors, were the most common ovarian neoplasms, with abdominal pain being a frequent initial symptom. Effective management often included surgery and chemotherapy. Breastfeeding and parity were significant protective factors and CA-125 was a prevalent tumor marker.

Association Between Heavy Metal Exposure and Central Nervous System Tumors: A Case-Control Study Using Single and Multi-Metal Models

(1) Background: Neoplasms of the central nervous system (CNS) encompass a cluster of malignant diseases originating from tissues or structures within the CNS. Environmental factors, including heavy metals, may contribute to their development. Therefore, this research was to investigate the association between heavy metal exposure and CNS tumor susceptibility using single and muti-metal models. (2) Methods: 63 CNS tumor patients and 71 controls were included. Urine samples from the CNS tumor patients and controls were analyzed for 47 metals using inductively coupled plasma-mass spectrometry in this study. Statistical analyses included conditional Wilcoxon rank-sum tests, logistic regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Bayesian Kernel Machine Regression (BKMR). (3) Results: In the single metal model, higher levels of seventeen metals might be associated with a lower incidence of CNS tumor, while higher exposure levels of five metals are associated with a higher incidence of tumor. LASSO regression selected nine metals for further BKMR analysis. The joint effects showed decreased tumor risk with increased metal mixture concentration. The level of the metals Ge, As, Rb, Zr, and Sn may be related to the incidence of meningiomas and gliomas. (4) Conclusions: This study explored the association between various metals and CNS tumors, providing ideas for future prospective cohort studies and laboratory studies, and providing a foundation for new ideas in the prevention and treatment of CNS tumors.

Gastric Epithelial Neoplasms in Patients with Pulmonary Arterial Hypertension Receiving Continuous Intravenous Prostacyclin Therapy

Background: The association of intravenous prostacyclin therapy, essential for improving prognosis and survival in pulmonary arterial hypertension (PAH), with gastric epithelial neoplasms is uncertain. This study aimed to analyze the clinicopathologic features of gastric neoplasms in patients with PAH undergoing continuous intravenous prostacyclin therapy. Methods: We screened the registry of patients with pulmonary hypertension who visited the NHO Okayama Medical Center. Of the patients with PAH managed between January 2003 and December 2022, those who underwent esophagogastroduodenoscopy (EGD) were assessed for gastric neoplasms. Their clinical, endoscopic, and histopathological data were reviewed. Results: Among the 186 patients with PAH, 56 underwent EGD, revealing 4 patients (aged 37–50 years) with gastric epithelial neoplastic lesions. All four patients received continuous intravenous prostacyclin therapy for a median of 151 months. Of the 98 patients who received prostacyclin, 28 patients underwent EGD; the incidence of gastric epithelial neoplasms was 4.1% (4/98) and the endoscopic detection rate was 14.3% (4/28). All patients had multiple tumors against a background of hypertrophic gastropathy (histologically being foveolar epithelial hyperplasia), with shared features of distal location, elevated morphology, and absent submucosal invasion. However, lymph node metastasis was observed in one lesion. By immunohistochemistry, the tumors exhibited gastric-predominant mucus phenotype and were managed by surgical or endoscopic resection without recurrence. Conclusions: The consistent clinicopathologic features of these cases suggest an association between continuous intravenous prostacyclin therapy and the development of hypertrophic gastropathy with potential progression to gastric epithelial neoplasia. Further prospective clinical trials are warranted to ensure safer prostacyclin use.

Comparison of Acute and Protracted Gamma Irradiation Effects During Perinatal Development in Beagle Dogs.

Ionizing radiation exposure during perinatal development can produce various biological effects on the developing offspring. These effects are dependent on a number of factors, including total dose, dose rate and the developmental processes occurring at the time of irradiation. The present study conducted an analysis of historical radiobiological archived data involving 60Co-gamma irradiation of beagle dogs at specific periods of prenatal or postnatal development. The original studies were performed at two sites where animals were exposed to a single, acute dose of 0.2 or 1.0 Gy at six different stages of perinatal development or with protracted exposures ranging from 0.004 to 0.35 Gy per day, over multiple days of gestation. A number of outcomes were investigated after perinatal irradiation including changes in sex ratio, survival probability, disease incidence and growth of animals, based on collected size and weight measurements of animals and different tissues. Protracted irradiations with doses up to 0.35 Gy per day did not significantly affect survival in animals when irradiated prenatally, although significant increases in the incidence of neoplasms and diseases related to the cardiovascular and urogenital system were observed at the time of death. Dogs irradiated at a dose rate of 0.10 Gy per day, with the irradiations continuing after birth and resulting in the accumulation of large total doses, were observed to have chronic radiation syndrome symptoms based on pathologies related to the hematopoietic system. Acute irradiation with 0.2 and 1.0 Gy resulted in changes of different body or tissue sizes measured in animals terminally, with changes detected after irradiation at all tested prenatal and postnatal time points, with the exception of irradiation at 365 days after birth. The present analysis provides new information regarding the biological effects of ionizing radiation during perinatal development in offspring in the unique mammalian study model of the beagle dog.

Search for Healthcare and Breast/Gynecological Cancer Prevention Among Brazilian Lesbian Cisgender Women

Although breast, cervical, endometrial, and ovarian cancers account for more than 43% of new cases in 2023 in Brazilian women, no national studies were found on the incidence, risk factors, and prevention of breast and gynecological neoplasms in lesbian women, causing the health needs of non-heterosexual women to go unnoticed by professionals. This study aims to identify and analyze the search for healthcare related to the prevention of breast/gynecological cancer among Brazilian lesbian cisgender women who have not had the disease. Seven lesbian women participated in this qualitative study. Semi-structured interviews were conducted and subsequently transcribed and analyzed following the reflexive thematic analysis approach and the theoretical framework of gender studies. Two thematic axes were constructed: gynecological appointments, which includes the subthemes follow-ups, types of exams, and struggles with the healthcare system, and meeting health professionals, which includes relationships with professionals, searching for professionals, discussing sexual orientation, and (un)preparedness. The participants in this study reported visiting a gynecologist at least once and doing preventive exams, although the frequency of these appointments varied for each woman. However, they highlighted that healthcare providers are not adequately prepared to address the needs of lesbian women and to talk about sexual orientation.

Chemopreventive role of β-caryophyllene in DMBA-induced skin cancer: Modulation of apoptotic pathways and PI3K/Akt signaling in Swiss albino mice.

The skin, with its robust structural integrity and advanced immune defense system, serves as a critical protective barrier against environmental toxins and carcinogenic compounds. Despite this, it remains vulnerable to the harmful effects of certain hazardous agents. This study aimed to investigate the chemopreventive potential of β-caryophyllene (BCP) in mitigating 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis, focusing on the modulation of apoptosis and PI3K/AKT signaling pathways. Swiss albino mice were utilized to assess the preventive effects of BCP in DMBA-induced skin cancer. Skin carcinogenesis was initiated by topical DMBA application, followed by promotion using croton oil. To evaluate the chemopreventive efficacy of BCP, a 50 mg/kg oral dose was administered 3 times a week for 16 weeks. The BCP treatment in DMBA-induced skin cancer mice significantly reduced tumor incidence, tumor burden and the total number of papillomas compared to untreated DMBA-exposed mice. Notably, BCP administration (p < 0.05) resulted in a marked increase in body weight and improvement in antioxidant enzyme activity. Additionally, BCP treatment led to significant reductions in lipid peroxidation and enhanced detoxification enzyme function. Histological examination of DMBA-induced skin tissues revealed the presence of keratin pearls, well-differentiated tumor cells and neutrophil infiltration. In contrast, BCP-treated mice showed only mild hyperplasia, dysplasia and moderate keratosis, suggesting a lower degree of tissue damage. Furthermore, BCP demonstrated a protective effect on liver histology, counteracting the toxic effects of DMBA exposure. Gene expression analysis revealed that BCP treatment significantly (p < 0.05) upregulated the pro-apoptotic genes Bax, p53, caspase-3 and caspase-9, while downregulating the anti-apoptotic Bcl-2 expression. Additionally, BCP treatment led to a marked reduction in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and PI3K/Akt signaling pathways, which are key regulators of cell proliferation and survival. This study provides compelling evidence that the antioxidant and pro-apoptotic effects of β-caryophyllene contribute to its chemopreventive properties in DMBA-induced skin carcinogenesis in mice. The modulation of key apoptotic signaling pathways and the suppression of the PI3K/Akt pathway by BCP underscores its potential as a therapeutic agent for preventing skin cancer. These findings pave the way for further exploration of BCP as a promising candidate for skin cancer prevention and therapy.

Oxidative Phosphorylation (OXPHOS) Promotes the Formation and Growth of Melanoma Lung and Brain Metastases.

Purpose: Melanoma mortality is driven by the formation and growth of distant metastases. However, the process and pathogenesis of melanoma metastasis remain poorly understood. Here, we interrogate the role of tumor oxidative phosphorylation (OXPHOS) in the formation of distant metastases in melanoma.Experimental Design: This study includes (1) new RNA-seq analysis of primary melanomas from patients characterized for distant metastasis events; (2) RNA-seq analysis and functional testing of genetic OXPHOS inhibition (PGC1α KO) the RCAS-TVA model, which is the only existing immunocompetent murine model of autochthonous lung and brain metastasis formation from primary melanoma tumors; and (3) functional experiments of genetic OXPHOS inhibition (NDUFS4 KO) in the B16-F10 and D4M-UV2 murine melanoma cell lines, including evaluation of subcutaneous, lung, and brain metastatic site dependencies.Results: OXPHOS was the most upregulated metabolic pathway in primary tumors that formed distant metastases in the RCAS-TVA mouse model of spontaneous lung and brain metastases, and in melanoma patients that developed brain or other distant metastases. Knockout of PGC1a in melanocytes in the RCAS-TVA melanoma mouse model had no impact on primary tumor formation, but markedly reduced the incidence of lung and brain metastases. Genetic knockout of a component of electron transport chain complex I, NDUFS4, in B16-F10 and D4M-UV2 murine melanoma cell lines did not impact tumor incidence following subcutaneous, intravenous, or intracranial injection, but decreased tumor burden specifically in the lungs and brain.Conclusions: Together, these data demonstrate that OXPHOS is critical for the formation of metastases in melanoma. Melanoma is the most aggressive form of skin cancer. One hallmark of this disease is a high risk of distant metastasis formation. The process and pathogenesis of metastasis in this disease remain poorly understood and there is controversy regarding the role of oxidative phosphorylation (OXPHOS) in melanoma metastasis. This study incorporates RNAseq analysis of primary melanoma tumors from patients characterized for distant metastasis events, RNAseq analysis of the only existing immunocompetent murine model of autochthonous lung and brain metastasis formation from primary melanoma tumors, and functional testing in multiple syngeneic models of melanoma at different tissue sites. This integrated analysis consistently demonstrates that melanoma OXPHOS promotes distant metastasis to the lungs and brain, two of the most common and clinically relevant sites of melanoma metastasis. This improved understanding of tumor OXPHOS may represent novel vulnerabilities for therapeutics development and surveillance/preventative strategies for melanoma metastasis.

Global, regional and national burden of neuroblastoma and other peripheral nervous system tumors, 1990 to 2021 and predictions to 2035: visualizing epidemiological characteristics based on GBD 2021.

Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, accounting for >15 % of cancer-related deaths in children. We analyzed the epidemiological statistical indicators of neuroblastoma and other peripheral nervous system tumors patients from 1990 to 2021 in Global Burden of Disease (GBD) 2021 database, aiming to provide valuable insights for public health interventions and clinical practices. Based on the GBD 2021 database, this study analyzed the incidence, mortality, prevalence, and Disability-Adjusted Life-Years (DALYs) of neuroblastoma and other peripheral nervous system tumors from 1990 to 2021, stratified by sociodemographic development index (SDI) and geographic regions. Cross-country inequalities analysis was conducted to quantify the SDI-related inequality of disease burden across countries. In addition, the average annual percentage change (AAPC) and Age-Period-Cohort (APC) model were used to evaluate the trend of disease burden, while the global burden of disease to 2035 was predicted by Bayesian Age-Period-Cohort (BAPC) model. This study reported the disease burden of neuroblastoma and other peripheral nervous system tumors in GBD 2021 database for the first time. Globally, the incidence and mortality of neuroblastoma have increased year by year from 1990 to 2021, especially in regions with low SDI, such as South Asia and sub-Saharan Africa, where the burden of disease has increased significantly. Regions with high SDI, such as North America and Western Europe, have seen a reduction in disease burden due to higher levels of medical care and earlier diagnosis. The age distribution shows that children under 5 years of age are mainly affected, especially in low- and middle-income areas. In addition, the incidence is slightly higher in men than in women. The BAPC model predicts that the global incidence, mortality, and DALYs of neuroblastoma will continue to increase until 2035. Significant regional and population variation in neuroblastoma and other peripheral nervous system tumors worldwide, with a particularly high disease burden in low SDI areas with limited medical resources. This trend highlights the urgent need for global public health interventions and resource allocation, particularly in low-income countries. Future research should focus on improving early diagnosis, risk stratification and target therapy in order to reduce the global burden of disease and improve patients' prognosis. This study was supported by National Natural Science Foundation of China (No. 82293662, No 82172357 and No 81930066), Key project of Shanghai "Science and Technology Innovation Action Plan (22JC1402304) and Research fund of Shanghai Municipal Health Bureau (No. 2019cxjq03).

Sequential transcriptome profiling: comparative analysis of normal and canine lymphoma preceding detailed T-cell and B-cell subtype comparison

IntroductionAs the lifespan of companion animals extends, the incidence of tumor also increases. Among these tumors, lymphoma is reported as the most prevalent hematopoietic tumor with a 80-90% prevalence rate. Ongoing research spans multiple domains, aiming to uncover novel therapeutic targets, including small molecular weight inhibitors, antibody treatments, and subtype-specific selective agents.MethodsTranscriptional profiling was performed on canine lymphoma samples to identify genes and functional pathways associated with pathogenesis, treatment response, and prognosis. Additionally, genes with potential relevance to the clinical characteristics of T-cell lymphoma (TCL), which is characterized by a low treatment response and poor prognosis, were identified through a comparative analysis of different lymphoma subtypes.ResultsWithin the canine lymphoma group, HERC5 showed consistent upregulation, a gene similarly implicated in human acute myeloid leukemia but previously no reports exist. Additionally, noteworthy genes, including IKZF2, CCL4, SAA1, and CD40, exhibited differential expression in the TCL group compared to the B-cell lymphoma (BCL) group.DiscussionThe upregulation of HERC5 may impact on canine lymphoma pathogenicity. Furthermore, the upregulation of IKZF2, CCL4, and SAA1, along with the downregulation of CD40, may contribute to adverse clinical characteristics of TCL in dogs.

A new weapon: the application of tumor vaccines based on extracellular exosomal heat shock proteins in immunotherapy

Despite the significant advancements in cancer research, innovative approaches are still needed to reduce tumor incidence, progression, and dissemination, as well as for prolonging patient survival. Currently, the development of cancer vaccines is gaining attention as a novel preventative and therapeutic strategy. Although the concept of cancer vaccination is not new, a limited number of vaccines have received approval for tumor therapy. Heat shock protein (HSP)-based vaccination represents a promising strategy that harnesses specific tumor antigens to activate immune responses. Exosomes (Exs) are highly heterogeneous bilayer vesicles capable of transporting various types of molecules through extracellular space. Compared with conventional anticancer drugs, exosomes exhibit low toxicity and good biocompatibility, and they can stimulate the immune system either directly or indirectly. Ex-based vaccines may elicit an antitumor immune response that generates memory cells capable of recognizing cancer antigens, thereby inhibiting disease progression. This paper reviews the potential applications of HSPs and exosomes in the prevention and treatment of solid tumors. Finally, we discuss the advantages of the extracellular exosomal heat shock protein (HSP-Ex1) vaccine and future research directions aimed at optimizing heat shock protein-based cancer immunotherapy strategies.

Chemoprotective Effect of Myrrhone against Diethylnitrosamine and Ferric Nitrile Induced Renal Cancer via Alteration of HO-1/Nrf2 and TRL4/NF-κB Signaling Pathway.

. Following a single dose of intraperitoneal DEN (200 mg/kg) and a twice-weekly administration of Fe-NTA, rats were administered either an oral dose of myrrhone (5, 10, or 15 mg/kg). The body weights and food intake of the rats were monitored at regular intervals, and the levels of renal cancer markers, antioxidants, inflammatory markers, and other parameters were assessed. Additionally, histopathological studies were conducted on the renal tissues, and the mRNA expression of Bax, Bcl-2, HO-1, SOD2, mtDNA, ATP8, PGC-1α, TRL4, and NF-κB was analyzed. . The dosage-dependent administration of myrrhone demonstrated a remarkable suppression of tumor incidence and an improvement in body weight and food intake. Myrrhone markedly decreased the level of ODC, Thymidine [3H] incorporation, and renal parameters such as creatinine, uric acid, BUN, Kim-1, Cysc-C, and LDH. Additionally, myrrhone significantly altered the levels of MDA, GSH, GPx, CAT, and SOD, as well as inflammatory cytokines such as TNF-α, INF-γ, IL-1β, IL-6, and IL-10, and inflammatory parameters such as COX-2, PGE2, TGF-β1, NF-κB, and iNOS. Furthermore, myrrhone significantly decreased the histopathological score and improved the condition of histopathology. Finally, myrrhone significantly altered the mRNA expression of Bax, Bcl-2, HO-1, SOD2, mtDNA, ATP8, PGC-1α, TRL4, and NF-κB. : The result clearly showed the chemoprotective effect of myrrhone against diethylnitrosamine and ferric nitrile induced Renal Cancer via alteration of HO-1/Nrf2 and TRL4/NF-κB Signaling pathway.