Cancer Investigation最新文献

Hepatocellular cancer (HCC), one of the world's most deadly tumors, and its incidence in the US continues to rise. Surgical resection/transplantation offers the only hope for cure; however, many patients are not candidates and have limited therapeutic options. Opioid growth factor (OGF) is a naturally occurring bioactive endogenous pentapeptide that inhibits growth of human HCC cell lines in vitro by a receptor-mediated mechanism and inhibits progression of tumors in nude mice. Based on these preclinical studies, we conducted a phase I clinical trial with dose escalation (standard 3 + 3 protocol) of OGF to determine the maximum tolerated dose in HCC patients with concomitant liver disease (NCT00706576). Fifteen doses were administered to 14 patients with a maximum 300 µg/kg dose. No Grade 3 toxicities were encountered in the study group. This dose exceeds the maximum tolerated dose reached in our previous phase I pancreatic cancer trial. We conclude that OGF can be safely administered to patients with HCC and concomitant liver disease without significant toxicities up to a dose of 300 µg/kg. The result of this trial provides data on toxicity and the pharmacokinetics of OGF in patients with HCC and liver disease and lays the groundwork for additional studies.

Background: Ovarian cancer (OC), the gynecologic malignancy with the poorest prognosis, is driven by metabolic reprogramming and dysregulated programmed cell death (PCD). However, their interplay and prognostic significance remain inadequately understood.

Methods: Transcriptomic data from OC patients and healthy controls (TCGA and GTEx) were analyzed to identify differentially expressed genes (DEGs) intersecting with metabolism-related (MRGs) and PCD-related genes (PCDRGs). Prognostic genes were determined using univariate Cox regression, LASSO, multivariate Cox regression, and stepwise analyses. Consensus clustering revealed enrichment differences, while a risk model and nomogram were developed for outcome prediction. Associations between prognostic genes, immune microenvironment, and drug sensitivity were also assessed.

Results: A total of 166 candidate genes were identified, with PLA2G2D, LPCAT3, ARG1, PLA2G4A, and EXOSC3 emerging as significant prognostic markers. The risk model demonstrated marked survival differences, while the nomogram showed robust calibration for survival prediction. Differential immune cell infiltration was observed between risk groups. Additionally, Sinularin and Fulvestrant exhibited variable sensitivity, validated through molecular docking models.

Conclusion: Metabolism-related PCD genes were identified as pivotal prognostic markers in OC, providing critical insights for prognostic evaluation and targeted therapy development.

Colon Cancer (CC) arises from abnormal cell growth in the colon, which severely impacts a person's health and quality of life. Detecting CC through histopathological images for early diagnosis offers substantial benefits in medical diagnostics. This study proposes NalexNet, a hybrid deep-learning classifier, to enhance classification accuracy and computational efficiency. The research methodology involves Vahadane stain normalization for preprocessing and Watershed segmentation for accurate tissue separation. The Teamwork Optimization Algorithm (TOA) is employed for optimal feature selection to reduce redundancy and improve classification performance. Furthermore, the NalexNet model is structured with convolutional layers and normal and reduction cells, ensuring efficient feature representation and high classification accuracy. Experimental results demonstrate that the proposed model achieves a precision of 99.9% and an accuracy of 99.5%, significantly outperforming existing models. This study contributes to the development of an automated and computationally efficient CC classification system, which has the potential for real-world clinical implementation, aiding pathologists in early and accurate diagnosis.

Background: Radiation-induced dermatitis, a common radiotherapy (RT) complication, affects 95% of breast cancer patients, with 10% experiencing severe reactions. Despite advancements, radiation dermatitis remains a challenge, disrupting treatment schedules and compromising patients' quality of life. Exploring herbal compounds, particularly Curcumin, has shown promise in addressing radiation-induced dermatitis, with its non-toxic and anti-inflammatory properties offering the potential for clinical trials to prevent these reactions.

Methods: This phase II randomized, double-blinded, placebo-controlled trial focused on adult females undergoing conventional fractionated RT. The main objective was to assess the efficacy of topical Curcumin in reducing the severity of radiation dermatitis.

Results: During a five-month study, 52 breast cancer patients completed the research. Participants were divided into Curcumin and placebo groups. In the first week, a significant difference in redness (P-value = 0.001) and irritation (P-value = 0.017) was observed, with the Curcumin group showing lower percentages. This trend continued in the second, third, and fourth weeks (P-value = 0.001). No statistical difference was found in itching (P-value = 0.446), and the occurrence of dryness (P-value = 1.000) remained constant in both groups throughout the four weeks. In pain the differences were significant in the second, third, and fourth weeks (P-value = 0.001).

Conclusion: The study highlights the success of a 2% Curcumin gel in reducing skin side effects during breast cancer radiation therapy, suggesting its potential to enhance patients' quality of life.

Trial registration: IRCT20181208041882N3, 06/11/2020 (https://en.irct.ir/trial/49228).

Genomic sequencing of tumours improves patient outcomes through implementation of precision oncology. At present, genomic testing is mainly confined to research settings, with samples sent to biopharmaceutical companies for analysis. The ever-expanding catalogue approved of targeted therapies has created an urgent unmet need for local genomic testing facilities, to enable upscaling of testing. Here, we compare the outcomes of local (IonTorrent^™) and commercial (Foundation Medicine) genomic testing collected from 30 cancer patients in from plasma and tissue samples. Overall concordance was high in both tissue (98%) and plasma (94.2%). Variants identified by both platforms had a strong correlation in variant allele frequencies (VAF%): plasma: r = 0.99 p < 0.0001, tissue: r = 0.91 p < 0.0001. However, numerous low VAF% variants resulted in low positive percentage agreement (tissue 78.8% plasma 16.1%) and positive predictive values (tissue 56.3% plasma 71.4%). Local sequencing demonstrated higher fidelity in detecting fusions but low fidelity in detecting indels. Overall, this study supports the use of local genomic testing for routine molecular diagnostics but highlights outstanding issues before widespread implementation. Processing of variants detected at low VAF% and the limit of detection of assays needs to be addressed. Construction of gene panels requires careful consideration, including incorporation of markers of genomic instability.

Background: Human immunodeficiency virus is associated with the development of various aggressive non-Hodgkin B-cell lymphomas (NHL). Despite this, people living with HIV (PLWH) are often excluded from clinical trials. Here we analyze the change in clinical trial exclusion among PLWH resulting from multilateral advocacy efforts since 2017.

Methods: We identified all US-based clinical trials with the keyword "lymphoma" with start dates between January 01, 2014 and January 04, 2025 using the publicly available NIH Clinical Trial Database (https://www.clinicaltrials.gov/). All studies with aggressive B-cell NHL subtypes were included. Regression models were performed to analyze descriptive factors.

Results: 1,973 US-based clinical trials were captured, of which 945 met criteria for further analysis. PLWH were excluded from 59% pre-2018 versus 48% post-2018. After multivariate adjustment, NIH-funded trials (24% exclusion rate, p < 0.001), other funders (64% exclusion rate), and studies initiated post-2018 (48% exclusion rate, p < 0.001) were associated with inclusion, while CAR-T-related studies (62% exclusion rate, p < 0.05) were associated with exclusion.

Conclusions: Likely partly due to advocacy from ASCO, NCI, and NCCN, there was a significant decrease in exclusion among PLWH in US-based NHL clinical trials. Future research should analyze the safety and efficacy of immunotherapy in PLWH to foster inclusion and reduce stigma among physicians and researchers.

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.

Accurate and timely diagnosis of t(9;22)-positive leukemias is vital to improving survival in pediatric patients. In low-resource settings, where healthcare disparities are exacerbated by limited resources, cost-effective and efficient diagnostic methods are essential for bridging these gaps and ensuring better outcomes. Among the diagnostic tools evaluated among 23 patients sample, RT-PCR demonstrated superior sensitivity (100%) and the shortest turnaround time (7 days), significantly outperforming FISH and karyotyping in both accuracy and timeliness. This capability of RT-PCR to provide reliable and rapid results enables earlier treatment initiation, which is critical in managing these aggressive leukemias. Simplified statistical reporting underscores RT-PCR's unmatched sensitivity, while FISH and karyotyping, though useful, showed moderate performance with longer delays. By adopting RT-PCR as the primary diagnostic tool in LMICs, healthcare systems can make faster and more accurate treatment decisions, reduce overall treatment costs by avoiding diagnostic delays, and ultimately improve survival rates in pediatric leukemia patients.