Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with ...locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.
Although advances in spatial transcriptomics (ST) enlarge to unveil spatial landscape of tissues, it remains challenging to delineate pathology-relevant and cellular localizations, and interactions ...exclusive to a spatial niche (e.g., tumor boundary). Here, we develop Cottrazm, integrating ST with hematoxylin and eosin histological image, and single-cell transcriptomics to delineate the tumor boundary connecting malignant and non-malignant cell spots in tumor tissues, deconvolute cell-type composition at spatial location, and reconstruct cell type-specific gene expression profiles at sub-spot level. We validate the performance of Cottrazm along the malignant-boundary-nonmalignant spatial axis. We identify specific macrophage and fibroblast subtypes localized around tumor boundary that interacted with tumor cells to generate a structural boundary, which limits T cell infiltration and promotes immune exclusion in tumor microenvironment. In this work, Cottrazm provides an integrated tool framework to dissect the tumor spatial microenvironment and facilitates the discovery of functional biological insights, thereby identifying therapeutic targets in oncologic ST datasets.
Background:
There is limited research exploring the psychological and social predictors of fear of cancer recurrence (FCR).
Objective:
This study tested the effects of social support, family ...resilience, and individual resilience on FCR among persons with breast cancer.
Methods:
A convenience sampling method was used to select 214 participants from March to August 2021 in 1 tertiary hospital in Jinan, China. Data were collected using self-administered questionnaires. Path analysis was adopted to explore the effects of social support, family resilience, and individual resilience on FCR.
Results:
Findings showed that 94.6% of the participants reached a clinical level of FCR. Social support (β = −.75, p < .01) and individual resilience (β = −.32, p < .01) negatively and directly impacted FCR. Family resilience indirectly impacted FCR through individual resilience (β = −.22, 95% confidence interval (CI): −.34 to −.08). Social support indirectly impacted FCR through family resilience and individual resilience (β = −.15, 95% CI: −.23 to −.06).
Conclusions:
Persons with breast cancer experienced a high level of FCR. Individual resilience was a mediator between family resilience and FCR. Resilience (individual resilience and family resilience) partially mediated the effects of social support on FCR. The findings indicate that measures focused on improving individual resilience, family resilience, and social support should be considered by nurses, which are helpful for easing FCR.
PURPOSE We aimed to systematically explore the value of iodine values calculated from dual-energy computed tomography (DECT) as potential prognostic factors for locally advanced gastric cancer (LAGC) ...patients undergoing neoadjuvant chemotherapy (NAC). METHODS Eighty-five LAGC patients were examined using DECT before and after NAC and were divided into responders and non-responders based on the tumor regression grade (TRG). The iodine values including portal- and delayed-phase iodine uptake (IU.sub.p and IU.sub.d, mg/mL) and total iodine uptake (TIU.sub.p and TIU.sub.d, mg) were acquired. Correlations between the reduction ratios of iodine values and TRG were analyzed. The diagnostic performance of parameters for differentiating responders from non-responders was calculated. Kaplan-Meier method was used for survival analysis. RESULTS The reduction ratios of total iodine uptake (%DELTATIU.sub.p and %DELTATIU.sub.d) were significantly correlated with TRG (P < .001). The ypN stage, %DELTATIU.sub.p, and %DELTATIU.sub.d were significant factors influencing progression-free survival (PFS) (P < .050). A value of %DELTATIU.sub.d less than or equal to 62.19% was associated with negative prognosis relative risk (RR):2.103; P = 0.021, as was ypN stage (RR: 4.250; P = .003). CONCLUSION Iodine values (especially the TIU) are noninvasive quantitative parameters that are potentially helpful for evaluating the treatment response and survival prognosis of LAGC after NAC. %DELTATIU.sub.d represents a strong independent prognostic factor, increasing preoperative risk assessment performance.
Aberrant expression of miR-106b is a specific symptom of many solid carcinomas. Overexpression of miR-106b has been observed in gastric cancer. The effect of miR-106b on gastric cancer has been ...investigated in different cell culture models. However, the effect of miR-106b on metastasis of early gastric cancer (EGC) remains unknown.
In the study, qRT-PCR, FISH, western blot, luciferase reporter assay, migration and invasion assays, flow cytometry and TUNEL staining were used to investigate the effect of miR-106b on metastasis of EGC.
To explore the function of miR-106b in EGC, we investigated the downstream signaling of miR-106b and found that ALEX1 was a direct target of miR-106 in gastric cancer cells. Up-regulation of ALEX1 effectively rescued the cell apoptosis induced by miR-106b inhibitor and promoted the expression levels of phosphorylation of JAK1 and STAT3. Moreover, overexpression of JAK1 reduced the cell apoptosis induced by miR-106b inhibitor and decreased the expression levels of the apoptotic proteins in gastric cancer cells. Furthermore, down-regulation of miR-106b promoted apoptosis of gastric cancer cells via inhibiting JAK1/STAT3 signaling pathway in vitro and in vivo. In addition, GLPG0643, a JAK1 inhibitor, enhanced the inhibitory effect of miR-106b inhibitor on gastric cancer growth in vivo.
These findings provided a potential therapeutic manner for the treatment of metastasis of EGC in clinic.
Abstract
Background
Important roles of INHBB in various malignancies are increasingly identified. The underlying mechanisms in gastric cancer (GC) microenvironment are still greatly unexplored.
...Methods
The clinical significance of INHBB and the correlation between INHBB and p-p65 in GC were assessed through analyzing publicly available databases and human paraffin embedded GC tissues. The biological crosstalk of INHBB between GC cells and fibroblasts was explored both in vitro and in vivo. RNA-seq analyses were performed to determine the mechanisms which regulating fibroblasts reprogramming. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify the binding relationship of p65 and INHBB in GC cells.
Results
Our study showed that INHBB level was significantly higher in GC, and that increased INHBB was associated with poor survival. INHBB positively regulates the proliferation, migration, and invasion of GC cells in vitro. Also, activin B promotes the occurrence of GC by reprogramming fibroblasts into cancer-associated fibroblasts (CAFs). The high expression of INHBB in GC cells activates the NF-κB pathway of normal gastric fibroblasts by secreting activin B, and promotes fibroblasts proliferation, migration, and invasion. In addition, activin B activates NF-κB pathway by controlling TRAF6 autoubiquitination to induce TAK1 phosphorylation in fibroblasts. Fibroblasts activated by activin B can induce the activation of p65 phosphorylation of GC cells by releasing pro-inflammatory factors IL-1β. p65 can directly bind to the INHBB promoter and increase the INHBB transcription of GC cells, thus establishing a positive regulatory feedback loop to promote the progression of GC.
Conclusions
GC cells p65/INHBB/activin B and fibroblasts p65/IL-1β signal loop led to the formation of a whole tumor-promoting inflammatory microenvironment, which might be a promising therapeutic target for GC.
Chordoid glioma (CG) of the third ventricle is a rare type of brain tumor. Here, we present a case, review of the literature and proposed a treatment strategy for this rare tumor. Here, A ...33-years-old woman presented with the menstrual disorder and progressive obesity. Magnetic resonance imaging showed a large irregularly circular tumor in the third ventricle. The tumor was subtotally resected by microsurgery via the right modified port approach. Immunohistochemical staining was positive for glial fibrillary acidic protein (GFAP), Vimentin and transcription termination factor-1 (TTF-1), and the Ki-67 proliferation index was low (5%), which indicating CG. Residual tumor decreased after treated by Gamma Knife radiosurgery (GKRS) with a dose of 15 Gy. During 30 months of follow-up, the tumor did not recur, and the patient suffered no complications. The diagnosis of CG requires a combination of clinical presentation, neuroimaging, and pathology. The ideal therapy is gross total resection (GTR) of the tumor. However, GTR is usually difficult and carries a high risk of postoperative complications because of the tumor location. This case indicates that planed subtotal resection followed by GKRS with a proper marginal dose could be a good treatment strategy for CG.
Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. ...Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.
A 19-year-old man presented with recurrent intermittent fever, progressive limbs weakness, numbness, and atrophy for 5 years. Biopsy of the sural nerve, spleen, lymph nodes, bone marrow and labial ...gland revealed that monomorphic small lymphoid cells infiltrated diffusely and that there was severe loss of large myelinated nerve fibers. Immunohistochemically, these cells were mainly CD8-positive T cells and were positive for CD3 and CD57. This patient was diagnosed as indolent CD8-positive T lymphoproliferative disorder (indolent CD8-positive T-LPD), emphasizing the need for a broad differential diagnosis under these conditions, and nerve biopsy should be performed.
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