Tumor Growth Rate Research Articles

Development of a Tumor Growth-responsive Robust Planning Method for Head and Neck Cancer in Carbon-ion Radiotherapy.

The current study aimed to evaluate a treatment planning method that is robust against tumor growth and to assess its effectiveness in particle therapy for head and neck cancer. The proposed method optimizes dose distribution by replacing the relative stopping power ratio (rSPR) of the clinical target volume (CTV) cavity region with a tumor-equivalent rSPR (Condition 1). The optimized initial treatment plan template was then recalculated using in-room CT images acquired in the same treatment position, and the doses to the tumor and organs at risk were compared with those in the initial treatment plan. We evaluated this method in 10 patients with head and neck cancer treated with carbon ion radiotherapy. To evaluate the effectiveness of the proposed method, we compared it to the initial treatment plan without the replacement (Condition 2). CTV V95% reduction relative to that of the initial treatment plan at the end of treatment was 1.3%±2.9% and 2.6%±3.7% for Condition 1 and Condition 2, respectively, with Condition 1 (Replacement condition) providing better CTV coverage. Subgroup analysis showed a higher change in target coverage in the mucosal melanoma than in the adenoid cystic carcinoma, suggesting that this was influenced by the rate of tumor growth. The proposed treatment planning method, which adjusts for tumor growth by modifying the rSPR in the cavity region, improved robustness in carbon ion radiotherapy for head and neck cancer. Condition 1 (with replacement) achieved better CTV coverage than Condition 2 (without replacement), particularly in fast-growing tumors like mucosal melanoma. This method ensures consistent dose delivery to tumors while maintaining safe doses to organs at risk, offering potential for improved treatment outcomes.

Guavira Fruit Pomace Promotes Immunomodulation and Reduction of Tumor Growth in Walker 256 Tumor-Bearing Rats

Background: Guavira fruit is widely used for juice extraction purposes, and this process generates large amounts of pomace (waste). Guavira pomace was dried and milled to produce guavira pomace flour (GPF), which is rich in antioxidants and dietary fibers (polysaccharides). These compounds are known for their immunomodulatory and antitumor effects. Objective: To investigate whether GPF intake promotes immunomodulation and reduces Walker 256 tumor growth in rats. Methods: GPF was provided to Wistar rats in two different models: 1) 15-day Model, according to which, Walker 256 tumor-bearing rats received GPF (63 mg/200 g b.w./day) simultaneously to tumor growth for 15 days; 2) 45-day Model, according to which, tumor-bearing rats received GPF for 30 days before tumor cell implantation, as well as during tumor growth - it totaled 45 days. After animals were euthanized, tumors were collected and weighed, and tumor cells were isolated for proliferation capacity determination ex vivo. Enzymatic/colorimetric methods were used to determine resident peritoneal macrophages’ functionality, whereas blood T and B lymphocytes were assayed for proliferation capacity, ex vivo, under stimuli. Results: The 15-day Model did not show tumor mass or cell proliferation reduction in the treated group. GPF stimulated macrophage response in tumor-bearing and non-tumor-bearing rats. However, there was a substantial reduction in tumor mass and tumor cell proliferation under the 45-day Model. Macrophage and lymphocyte response decreased; it suggested that GPF can directly act in the tumor. Conclusion: Based on these findings, GPF has immunomodulatory and antitumor actions, and ingestion time plays a key role in them.

Preoperative Tumor Growth Rate Does Not Predict Overall or Progression-free Survival in Patients With Glioblastoma.

Presurgical tumor volume progression in glioblastoma (GBM) may be a predictor of survival. This study aims to evaluate the potential impact of preoperative tumor growth and other clinical as well as laboratory parameters on overall survival (OS) of GBM patients. We retrospectively analyzed 98 adult patients with GBM who received two magnetic resonance imaging (MRI) scans between 2013 and 2023, before primary surgery and concurrent Stupp chemoradiotherapy. Tumor growth rates were calculated to classify GBM into slower and faster growing categories. Statistical analyses, including Kaplan-Meier and multivariable Cox regression survival analyses, were performed to evaluate the impact of various clinical and treatment-related factors on OS and progression-free survival (PFS). Slower growing tumors had a significantly longer doubling time than faster growing lesions. Univariable analysis showed no significant differences in OS (p=0.12) or PFS (p=0.4) when analyzed according to tumor growth. When stratified by O6-methylguanin-DNA-methyltransferase (MGMT) status, there were still no differences in OS (p=0.14), but in PFS (p=0.009). In the multivariable Cox regression analysis, radiation dose (p=0.02) and the number of adjuvant cycles of temozolomide (TMZ) (p=0.002) were significantly associated with OS. MGMT status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with prolonged PFS. Specific volume growth rate (SVGR), patient age, baseline tumor volume, Karnofsky performance status, extent of resection, and total radiation dose were not significantly associated with PFS. SVGR was not significantly associated with OS or PFS. In contrast, MGMT status, radiation dose, and number of adjuvant TMZ cycles were identified as predictors of treatment outcomes. These factors can guide physicians when designing personalized treatment concepts for patients with GBM.

Establishing a Mandibular Osteosarcoma Model in SD Rats Using Tissue Block Transplantation.

To investigate the feasibility of establishing a mandibular osteosarcoma model in Sprague-Dawley (SD) rats using tissue block transplantation, providing a foundational model for osteosarcoma research. Fourteen male SD rats, 3 weeks old and SPF grade, were randomly divided into a control group (n=4) and a mandibular osteosarcoma group (n=10). Using tissue block transplantation, UMR106 cell-induced tumor tissues were transplanted subcutaneously into the left mandibular marrow cavity of the SD rats. Observations included behavioral changes, weight variations, tumor growth, and tumor formation rate. Bone changes were monitored via micro-CT scanning, and histological analysis was conducted using HE staining. Two weeks post-transplantation, the mandibular osteosarcoma group exhibited significant left facial swelling, malocclusion, eating difficulties, and weight loss compared to the control group. The tumor formation rate was 80% (8/10). Micro-CT scans indicated significant bone destruction in the osteosarcoma group. HE staining revealed high cellular atypia and pathological mitoses in both subcutaneous and mandibular osteosarcoma cells, with no notable abnormalities in lung tissues. Tissue block transplantation is a viable method to establish a mandibular osteosarcoma model in SD rats. This method is simple, with a high tumor formation rate, providing an ideal animal model for mandibular osteosarcoma research.

Banxia xiexin decoction prevents the development of gastric cancer.

In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown. To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, in vivo and in vitro experiments. The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments. All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. In vitro cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of EGFR, PIK3CA, IL6, BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression. BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

Follow-up analysis of lesion characteristics of enchondromas and atypical cartilaginous tumours of the knee and shoulder region on MRI.

Enchondromas (ECs) and atypical cartilaginous tumours (ACTs), respectively, represent benign and intermediate cartilaginous bone tumours. Differentiation between these tumour entities bears difficulties, as histology and MRI cannot always provide exact diagnoses. Observation of the natural course of ECs/ACTs via follow-up MRIs might support tumour distinction without needing biopsy harbouring sampling error. Reports of patients that had undergone MRI exams of the knee (n = 44.762) or shoulder (n = 21.550) at a single radiology institute between 01.01.2007 and 01.03.2020 were searched for ECs/ACTs with at least one follow-up MRI. Scans of 176 patients (with 182 cartilage lesions) fulfilling these criteria were subsequently re-examined together with corresponding MRI reports to evaluate morphological tumour development over time, focusing on potential alterations of lesion size, tumour-related oedema, and scalloping. Median follow-up time was 27 ± 53 months for knee tumours and 26 ± 32 months for shoulder lesions. Presence of tumour growth was significantly higher in ACTs than in ECs both at the knee (p = 0.04) and shoulder (p = 0.03). While ACTs were associated with median tumour growth rates of 0.039 mm/month (knee) and 0.083 mm/month (shoulder), ECs of the knee and shoulder showed lower median growth rates equivalent to 0.0 mm/month (p < 0.01, p < 0.01). ECs and ACTs both presented stable regarding tumour-related oedema and scalloping during follow-up. ACTs and ECs show different tumour growth rates. Growth rates are slow for both, ECs and ACTs, supporting the current concept of watchful waiting. ECs may decrease in size. Follow-up MRIs may support the radiological differentiation of cartilage lesions. Question Both singular MRI and histological examination have limitations regarding differentiation of enchondromas (EC) and atypical cartilaginous tumours (ACTs). Findings Median ACT growth rates were 0.039 mm/month (knee) and 0.083 mm/month (shoulder), while median growth rates of EC in the knee and shoulder were 0.0 mm/month. Clinical relevance Active surveillance is a safe strategy when dealing with ECs and ACTs of the long bones; follow-up MRIs may support tumour distinction of cartilage lesions, as ECs and ACTs show different growth behaviour.

7428 Clinical and Radiological Characterization and Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity &amp;gt;10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was &amp;gt;60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p&amp;lt;0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

7323 Prostatic Acid Phosphatase Is Negatively Regulated by Androgens and Persists in Castration-resistant Prostate Cancer

Abstract Disclosure: A. Kirschenbaum: None. P. Cheung: None. S. Yao: None. P. Cheung: None. Background: Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic PCa respond initially to androgen deprivation therapy (ADT) but the majority will progress to lethal, metastatic, castrate-resistant PCa (mCRPC). The identification of markers of mCRPC that are not regulated or negatively regulated by androgens can serve as markers and therapeutic targets in mCRPC. We hypothesized that prostatic acid phosphatase (PAP), a protein phosphatase and 5’ectonucleotidase that is expressed in both the cytoplasm and transmembrane (TM-PAP) of PCa cells, is negatively regulated by androgen signaling and can serve as a therapeutic target. Methods: PAP protein expression was assessed by immunohistochemistry (IHC) in PCa cell line spheroids (VCaP, 22Rv1, LNCaP, C42B) +/- androgen addition as well as in LNCaP s.c. xenografts +/- castration. Protein expression of PAP was assessed with western blotting in PCa cell lines after treatment with androgens (DHT) and anti-androgen (enzalutamide). Results: In spheroids derived from PCa cell lines, there is some IHC expression of PAP with the strongest staining in VCaP and 22Rv1 spheroids. DHT decreased PAP IHC expression in all spheroids. LNCaP and VCaP s.c. xenografts demonstrated that castration decreased tumor growth rates but that in castrate as well as control tumors PAP expression persisted. All forms of PAP including TM-PAP are expressed in VCaP cell line and were negatively regulated by androgen addition. Conclusions: The identification of markers of mCRPC that are not regulated or are negatively regulated by androgen could help identify recalcitrant tumor cells and mount targeted delivery of therapeutic agents. In several androgen sensitive PCa cell lines, DHT addition decreased PAP expression in spheroids. In vivo, PAP expression persists after castration in spite of decreases in tumor growth rates. Finally, DHT decreases and enzalutamide restores PAP expression in vitro. These data demonstrate that PAP is a more progenitor cell marker in PCa that persists after castration and may be targeted in castration-resistant disease. Presentation: 6/3/2024

9294 Clinical and Radiological Characterization And Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity &amp;gt;10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was &amp;gt;60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p&amp;lt;0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

Metabolic Rate and Oxidative Stress as a Risk Factors in the Development of Colorectal Cancer.

There is growing evidence that the body's energy expenditures constitute a significant risk factor for the development of most deadly diseases, including cancer. Our aim was to investigate the impact of basal metabolic rate (BMR) on the growth and progression of colorectal cancer (CRC). To do so, we used a unique model consisting of three lines of laboratory mice (Mus musculus) artificially selected for high (HBMR) and low (LBMR) basal metabolic rate and randomly bred individuals (non-selected, NSBMR). The experimental individuals were implanted with human colorectal cancer cells DLD-1. The variation in BMR between the lines allowed for testing the impact of whole-body metabolism on oxidative and antioxidant parameters in the liver throughout the cancerogenesis process. We investigated the dependence between metabolic values, reactive oxygen species (ROS) levels, and Kelch-like ECH-associated protein 1-based E3 ligase complexes (Keap1) gene activity in these animals. We found that the HBMR strain had a higher concentration of oxidative enzymes compared to the LBMR and NSBMR. Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and Keap1 expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR.

8024 A Case of Smoldering Clinically Silent Cushing’s Disease

Abstract Disclosure: C. Bheeman: None. I. Shafiq: None. Aggressive pituitary adenomas account for about 10% of all pituitary adenomas. These aggressive tumors are noted to have unusually rapid tumor growth rate despite optimal standard therapies including surgery, medical therapy and radiotherapy. We present a case of a 39-year-old female with no prior past medical history who initially presented with complaint of amenorrhea. She had reported she had not menstruated for the past 6 months. She also endorsed galactorrhea with nipple stimulation. A pituitary dedicated MRI revealed a pituitary adenoma measuring 2.5 x 1.7 x 1.7 cm. Hormonal work-up showed salivary cortisol on two consecutive nights that was 66 ng/dL and 52 ng/dL (reference range: 0 - 99 ng/dL) and a prolactin that was slightly elevated at 44.9 ng/mL (reference range: 4.8-23.3 ng/mL). This elevation in prolactin was thought to be due stalk effect and since her hypothalamus-pituitary-gonadal axis was suppressed, patient had a transsphenoidal resection of what was thought to be a nonfunctioning adenoma. However, the pathology of her tumor was significant for extensive ACTH staining and a Ki-67 of 11 - 15%. Her clinical course proved to be challenging as her tumor reoccurred multiple times and she eventually developed biochemical and clinical evidence of Cushing’s disease and had visual defects due to compression of the tumor on the optic nerves. This tumor was refractory to multiple surgeries, radiation treatment and chemotherapy. Through the presentation of this case, we aim to highlight the factors associated with aggressive pituitary adenomas, the current treatment guidelines and emerging medical therapies. Presentation: 6/1/2024

Calibrating tumor growth and invasion parameters with spectral spatial analysis of cancer biopsy tissues

The reaction-diffusion equation is widely used in mathematical models of cancer. The calibration of model parameters based on limited clinical data is critical to using reaction-diffusion equation simulations for reliable predictions on a per-patient basis. Here, we focus on cell-level data as routinely available from tissue biopsies used for clinical cancer diagnosis. We analyze the spatial architecture in biopsy tissues stained with multiplex immunofluorescence. We derive a two-point correlation function and the corresponding spatial power spectral distribution. We show that this data-deduced power spectral distribution can fit the power spectrum of the solution of reaction-diffusion equations that can then identify patient-specific tumor growth and invasion rates. This approach allows the measurement of patient-specific critical tumor dynamical properties from routinely available biopsy material at a single snapshot in time.

Impact on Prognosis of Stage I Non-Small Cell Lung Cancer Secondary to Delays in Diagnostic Workup.

Background Diagnostic workup of small pulmonary nodules often requires follow-up CT scans to confirm nodule growth before invasive diagnostics or treatment. Purpose To confirm prior results from the International Early Lung Cancer Action Program (I-ELCAP) on quantifying decreases in lung cancer prognosis by using two large databases, the National Lung Screening Trial (NLST) and International Association for the Study of Lung Cancer (IASLC). Materials and Methods In this retrospective study, a model was developed to predict cure rates based on size of solid nodules using the NLST (August 2002 to summer 2007) and IASLC (January 2011 to December 2019) databases, focusing on stage I non-small cell lung cancer (NSCLC). Kaplan-Meier methods were used to calculate 10-year lung cancer-specific survival and 5-year overall survival rates for different tumor sizes. Tumor diameter increases after 90-, 180-, and 365-day delays were estimated using volume doubling times (VDTs) of 60, 120, and 240 days corresponding to fast, moderate, and slow tumor growth. Initial and delayed lung cancer cure rates were assessed across nine scenarios of time delays and tumor growth rates and compared with the previous results of the I-ELCAP database. Results Using regression models based on 166 NLST and 22 590 IASLC patients with NSCLC, 10-year lung cancer-specific survival and 5-year overall survival, respectively, for tumors 4.0-20.0 mm in diameter were estimated. For a 20.0-mm tumor with a 60-day VDT in the NLST database, the lung cancer-specific survival decreased from 83.4% to 76.5%, 66.8%, and 32.3% after 90, 180, and 365 days, respectively. The IASLC database showed similar decreases in 5-year overall survival, from 81.2% to 73.4%, 62.4%, and 23.3% after 90, 180, and 365 days, respectively. Comparison across NLST, IASLC, and I-ELCAP databases revealed minor variations in lung cancer cure rates between 79.9% and 83.4%, with reductions of 6.9%-8.3% after a 180-day delay with a 120-day VDT. Conclusion The NLST and IASLC databases confirmed prior estimates from the I-ELCAP database for the decrease in lung cancer prognosis due to diagnostic delays. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Park and Lee in this issue.

PD-L1 in melanoma and extracellular vesicles promotes local and regional immune suppression through M2-like macrophage polarization.

Tumor-associated macrophages (TAMs) exhibit dual roles in tumor progression. TAMs are known to induce PD-L1 expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored. Herein, our findings indicated that CD163 and MRC1 levels were significantly elevated in metastatic melanomas compared to primary melanomas, correlating with CD274 expression and predicted patient clinical outcomes. To study the mechanisms regulating M2-like polarization, PD-L1 was knocked out in both YUMM1.7 and B16-F10 melanoma cells. The data revealed that knocking out PD-L1 (PD-L1KO) in melanoma resulted in a decelerated in vivo growth rate, accompanied by a significantly increased M1/M2 ratio, more dendritic cells, and enhanced activation of CD8+ T cells compared to wild-type (WT) melanoma cells. These alterations were associated with decreased expression of M2-associated chemokines (CCL2, CCL3, and CXCL2) and cytokines (IL6, IL10, and TGFβ1). Mice harboring PD-L1KO melanomas exhibited elevated levels of CD8+ T cells in both the tumor-draining lymph nodes and the bloodstream, compared to mice with PD-L1WT melanomas. Treatment with extracellular vesicles (EVs) derived from PD-L1KO melanoma resulted in a reduced tumor growth rate and fewer M2-like macrophages in the tumors compared to EVs from PD-L1WT melanomas. Therefore, our data suggest that PD-L1 in melanoma and melanoma-derived EVs induces M2-like polarization, contributing to local and regional immune suppression.

Effects of generational low dose-rate 137Cs internal exposure in descendant mice

To quantitatively investigate the effects of chronic low-dose internal exposure to Cesium-137 on DNA damage, carcinogenicity, and offspring over multiple generations. The potential genetic risk in humans was predicted based on next-generation murine mutation rates to confirm the reasonableness of the current Cesium-137 dose limits for food. Cesium-137 (100 Bq/mL) was provided in drinking water to A/J mice, facilitating chronic, low-dose, low-dose-rate internal exposure through sibling mating over 25 generations (G25). The A/J mice were compared with a control strain with the same origin ancestry (no Cesium-137 water) for DNA double-strand breaks (DSBs), oxidative stress, chromosome aberrations, micronucleus test results, whole genome analysis, carcinogenicity, tumor growth rate, and immune competence. Compared to the control group, DNA DSBs and oxidative stress were significantly increased in the Cesium-137 group. However, no significant differences were observed between the groups regarding chromosome aberration, micronuclei, or the whole genome sequence mutation analysis. Although the carcinogenic rate did not differ between the groups, the rate of tumor growth was significantly suppressed in the Cesium-137 group. The anti-tumor cytokine trend in the Cesium-137 group likely contributed to this effect. No pathological or genetic effects were observed in the offspring of mice drinking water containing 100 Bq/mL Cesium-137 after G25. The contribution of low dose-rate radiation to carcinogenicity was not additive but growth-inhibitory. Although the negative data are not conclusive, these findings are deemed highly reliable.

Cu0-based nanoparticles boost anti-tumor efficacy via synergy of cuproptosis and ferroptosis enhanced by cuproptosis-induced glutathione synthesis disorder

Apoptotic resistance of tumor often leads to poor efficacy from mono-therapy based on apoptosis. Cuproptosis, a new type of non-apoptotic cell death related to mitochondrial dysfunction, can alter metabolism and enhance ferroptosis, providing a promising strategy for effective synergistic cancer treatment. In this work, Cu0-based nanoparticles (denoted as HA-ZCu) were successfully developed to improve anti-tumor efficacy by combining cuproptosis with enhanced ferroptosis, which was achieved by cuproptosis-induced glutathione synthesis disorder. In vitro studies revealed that HA-ZCu effectively induced cuproptosis and ferroptosis in HepG2 cells. Moreover, HA-ZCu induced mitochondrial dysfunction and decreased intracellular adenosine triphosphate (ATP), glutamate, and glutathione, demonstrating the effective synergy. In vivo studies further approved the synergistic therapeutic efficacy of HA-ZCu, where the inhibition rate of tumor growth reached 83.2 %. This work represents the first example of enhanced anti-tumor efficacy via cuproptosis and ferroptosis synergy through cuproptosis-induced glutathione synthesis disorder.

Prognostic Impact of Tumor Growth Rate During Second-line Chemotherapy in Patients With Gastric Cancer.

Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50years) and intervals (2/5/10years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20mm in size, and the deep submucosal invasion rate was less than 30%. A mathematical simulation model revealed that screening every 5years starting at 45years of age could efficiently assist in identifying HpNGNs at an early stage.

Correlation of Immunomodulatory Cytokines with Tumor Volume and Cerebrospinal Fluid in Vestibular Schwannoma Patients.

Sporadic vestibular schwannomas (VSs) often exhibit slow or negligible growth. Nevertheless, some VSs increase significantly in volume within a few months or grow continuously. Recent evidence indicates a role of inflammation in promoting VS growth. Therefore, our study aimed to identify cytokines, which are associated with larger VSs. The expression of different cytokines in VS tumor samples and VS primary cultures was investigated. Additionally, the concentration of cytokines in cell culture supernatants of VS primary cultures and cerebrospinal fluid (CSF) of VS patients and healthy controls were determined. Correlation analysis of cytokine levels with tumor volume, growth rate, Koos grade, age, and hearing was examined with Spearman's-rank test. The mRNA expression of CC-chemokine ligand (CCL) 18, growth differentiation factor (GDF) 15, and interferon regulatory factor 4 correlated positively with tumor volume. Moreover, the amount of GDF15 in the cell culture supernatant of primary cells correlated positively with tumor volume. The concentrations of the cytokines CCL2, CCL5, and CCL18 and transforming growth factor beta (TGFB) 1 in the CSF of the patients were significantly different from those in the CSF controls. Inhibition of immune cell infiltration could be a putative approach to prevent and control VS growth.

Innovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.

Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.