Journal of cancer research and therapeutics最新文献

Abstract: Mature cystic teratoma (MCT) is the most common germ cell tumor of the ovary, comprising 20% of all ovarian neoplasms. Malignant transformation (MT) is an uncommon complication and occurs in approximately 1-3% of all MCTs. The most common histological type of MT is squamous cell carcinoma. Other rare transformations include - carcinoid tumors, melanoma, adenocarcinoma, and sarcoma. We present one such rare case of bilateral MCT with unilateral MT into mucinous adenocarcinoma of intestinal type.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. The mechanisms underlying metastasis, which contributes to poor outcomes, remain elusive.

Methods: We used the Cancer Genome Atlas dataset to compare mRNA expression patterns of integrin α6 (ITGA6) and integrin β4 (ITGB4) in patients with CRC. We measured ITGA6 and ITGB4 expression levels in highly metastatic (i.e., HCT116 and SW620) and lowly metastatic (i.e., SW480 and Caco2) CRC cell lines. Exosomes were isolated from cell culture media and characterized using western blotting and nanoparticle analyses. The role of exosomes in lung metastasis was investigated using xenograft experiments in mice models, which received CRC cell injection and were treated with exosomes.

Results: ITGA6 and ITGB4 were significantly overexpressed in CRC tissues, and ITGA6 was associated with the American Joint Committee on Cancer (AJCC) stage and outcome. ITGA6 and ITGB4, as well as exosomal ITGA6 and ITGB4, were significantly more highly expressed in HCT116 and SW620 cells than in SW480 and Caco2 cells. The proliferation and tubulogenesis of vascular endothelial cells were markedly decreased by disruption of ITGA6 and ITGB4 but were markedly increased by ectopic expression of ITGA6 and ITGB4. Exosomal ITGA6 and ITGB4 promoted CRC metastasis to the lung in vivo.

Conclusions: Taken together, our findings suggested that exosomal ITGA6 and ITGB4 displayed organotropism to the lung and upregulated proliferation and tubulogenic capacities, which might help reduce lung metastasis from CRC. These findings provided new insights into the mechanisms of CRC metastasis and provided novel potential therapeutic targets.

Introduction: Cancer cachexia (CC) is characterized by weight loss with specifically reduced skeletal muscles and adipose tissues in patients with late-stage cancer. Dihydroartemisinin (DHA), an effective antimalarial derivative of artemisinin, has been demonstrated to have anti-inflammatory and antitumor properties.

Materials and methods: This study examined the effects of DHA on the Lewis lung carcinoma (LLC)-induced CC mouse model.

Results: DHA treatment significantly increases tumor-free body weight and food intake but decreases serum interleukin-6 level and tumor weight in CC mice. In addition, DHA treatment relieves muscle atrophy and decreases muscle ring finger 1 (MuRF1) and F-box-only protein 32 (Fbx32) expressions in CC mice. In vitro, DHA reverses the reduction in myotube formation induced by an LLC-conditioned medium and increases Fbx32 expression in C2C12 mouse myotubular cells.

Conclusions: Our study demonstrated that DHA ameliorates the cachectic state and skeletal muscle atrophy in LLC-induced cachectic mouse models, suggesting its therapeutic potential for CC.

Background: The low incidence and poor prognosis primary trastuzumab resistance (PTR) in HER2-positive breast cancer has limited research into possible treatments. Thus, it remains unclear whether this group of patients could benefit from nontargeting HER2 antiangiogenic therapy.

Patients and methods: We collected the medical data for HER2-positive patients with PTR who received apatinib 250 mg and trastuzumab-based chemotherapy (ATBC) between March 18, 2017, and March 31, 2022. All patients had progressed on ≥2 anti-HER2 treatments, including trastuzumab and small molecular tyrosine kinase inhibitors. We evaluated tumor response and safety profiles to ATBC over a median follow-up time of 34.5 months.

Results: A total of 198 consecutively HER2-positive metastatic breast cancer patients were reviewed; 20 were PTR and received ATBC. The clinical benefit rate of the total cohort was 55.0%. No patient showed a complete response. The median PFS and overall survival (OS) of the entire cohort was 5.7 months (95% CI 2.9-8.5) and 24.6 months (95% CI 6.9-42.4), respectively. The estimated 2-year survival rate was 46.7% (95% CI 38.4-81.6%). The most common nonhematologic adverse events were hypertension (70.0%), hand-foot skin reaction (55.0%), proteinuria (40.0%), and cardiovascular decrease of LVEF (20.0%). No new toxicities were observed.

Conclusion: ATBC had favorable effects for PTR breast cancer patients in later line treatment. The toxicity of the triple-combination regimen was tolerable; thus, further research should focus on identifying PTR patients who could benefit from ATBC.

Background: Cryoablation induces antitumor immune responses. Spatial transcriptomic landscape technology has been used to determine the micron-level panoramic transcriptomics of tissue slices in situ.

Methods: The effects of cryoablation on the immune microenvironment in non-small cell lung cancer (NSCLC) were explored by comparing the Whole Transcriptome Atlas (WTA) panel of immune cells before and after cryoablation using the spatial transcriptomic landscape.

Results: The bioinformatics analysis showed that cryoablation significantly affected the WTA of immune cells, particularly genes related to cellular components, biological processes, molecular functions, proliferation and migration, and cytokine-cytokine receptor interaction signaling pathways.

Conclusions: The findings of this study suggest that cryoablation significantly impacts the biological functions of immune cells in the tumor microenvironment of NSCLC through multiple mechanisms.

Objective: This retrospective study aimed to determine the need for lymph node resection during surgical treatment in patients with stage IA non-small-cell lung cancer (NSCLC).

Materials and methods: A total of 1428 patients diagnosed with cT1N0M0 1 A stage NSCLC who underwent surgery were divided into two groups: lymphadenectomy (n = 1324) and nonlymphadenectomy (n = 104). The effects of lymph node resection on overall survival (OS) and recurrence-free survival (RFS) and on clinicopathological factors that affected the prognosis of the patients were investigated.

Results: The group that underwent lymph node resection had a better 5-year OS (89.2% vs 81.1%) and 3-year RFS (87.6% vs 79.2%) than the one that did not. Multivariate Cox regression analysis revealed that the risk of OS in the nonlymphadenectomy group increased by 72% compared to that in the lymphadenectomy group [hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.08-2.74; P < 0.05]. The risk of RFS in the group without lymphadenectomy increased by 45% compared to that in the group with lymphadenectomy (HR, 1.45; 95% CI, 0.98-2.14;P = 0.06). Significant reductions in the OS (HR, 5.90; 95% CI, 1.80-20.00; P < 0.005) and RFS (HR, 4.00; 95% CI, 1.50-11.00;P < 0.005) can be seen in the absence of lymph node resection in NSCLC patients with emphysema.

Conclusion: A thorough evaluation and removal of the hilar and mediastinal lymph nodes may prove useful in determining the cancer stage and assessing the need for further treatment, thus enhancing the prognosis of patients with stage IA NSCLC.

Objective: To evaluate the postoperative complications and prognosis of renal cell carcinoma (RCC) in a solitary kidney after irreversible electroporation (IRE).

Materials and methods: A total of 8 patients with 9 RCCs in a solitary kidney treated with computed tomography (CT)-guided IRE from February 2017 to September 2020 were retrospectively analyzed. Follow-up included contrast-enhanced CT or magnetic resonance imaging examinations at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and each year after IRE and the evaluation of the incidence of postoperative complications, renal function changes, local tumor recurrence, and metastasis.

Results: Technical success was achieved in all 8 patients treated with IRE. No serious complications were observed. Recurrence or metastasis occurred in two patients. The renal function and hemoglobin values of the 8 patients before treatment and at the last follow-up showed no significant difference.

Conclusion: IRE is a relatively effective, safe, and feasible treatment for RCCs in a solitary kidney, which improved the effective survival and quality of life of these patients.

Abstract: Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results. Therefore, we reviewed the interactions between immune-infiltrating subtypes and tumor cells throughout the entire TME. By examining the antitumor or protumor effects of each TIL subtype, we aimed to better characterize the tumor immune landscape, offering more accurate and comprehensive insights for guiding triple-negative breast cancer (TNBC) treatment. In addition, this approach could lead to the development of new therapeutic targets, enabling tailored treatment strategies and precision medicine. Accumulating evidence suggests that the intestinal microbiome and its metabolites influence antitumor responses by modulating innate and adaptive immunity, with specific bacteria potentially serving as biomarkers for predicting clinical responses. Various studies have identified microorganisms in breast tissue, previously considered sterile, revealing differences in breast microbial composition between patients with breast cancer and controls, as well as associations between specific breast microorganisms and clinicopathologic features, including immune correlations. The aim of this review was to provide a more comprehensive set of prognostic markers for TNBC and to tap into potential-specific therapeutic targets.

Objective: Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range.

Methods: This retrospective study scrutinized 2,167 cases of stage II CRC verified by pathology after surgery at the Fudan University Shanghai Cancer Center. Using R software to calculate the optimal critical value to compare the clinical and pathological characteristics and prognosis of different levels of tumor markers. The survival and regression modeling strategies packages of R software drew the nomograms.

Results: Utilizing R software, the optimal critical value of CA19-9 was determined as 12.12 U/mL and that of CEA as 1.89 U/mL. Kaplan-Meier survival analysis unveiled that, within the normal range, higher levels of CEA were linked to poorer overall survival (OS) [HR = 1.829 (1.280, 2.989), P = 0.0033] and disease-free survival (DFS) [HR = 1.472 (1.114, 1.944), P = 0.0444]. Similarly, heightened levels of CA19-9 also indicated inferior OS [HR = 1.750 (1.203, 2.455), P = 0.0076] and DFS [HR = 1.361 (1.098, 1.686), P = 0.0049]. Furthermore, multivariate analysis identified CA19-9 as an independent risk factor for OS (HR = 1.49,95% CI: 1.086-2.045, P = 0.014) and DFS (HR = 1.327,95% CI: 1.070-1.647, P = 0.01), while the impact of CEA on OS and DFS was not statistically significant. A nomogram constructed based on the Cox regression model can effectively evaluate the prognosis of CRC patients.

Conclusion: Although within the normal range, elevated CA19-9 was associated with an inferior prognosis, chemotherapy decisions of different intensities can be adjusted based on nomograms. This work will contribute to standardizing the diagnosis and treatment of stage II CRC and provide clinicians with essential insights for chemotherapy decisions.

Background: Endoscopic submucosal dissection (ESD) is a standardized procedure for intramucosal and slightly invasive submucosal colorectal cancers (CRC). However, the role of ESD for T1b (depth of submucosal invasion: ≥1,000 μm) CRC remains unclear. This study aimed to investigate the long-term efficacy and safety of ESD for T1b CRC.

Methods: This study involved 50 patients with T1b CRC who underwent ESD, including 31 who received subsequent surgery (ESD + surgery group) and 19 who reported comorbidities or refused subsequent surgery (ESD-alone group). The clinical outcomes, lymph node metastasis (LNM) rate, and recurrence and survival rates were determined.

Results: All the patients achieved en-bloc resection, and 41 patients achieved R0 resection. The mean tumor diameter was 31.2 ± 11.9 mm. LNM was detected in 3 (6%) cases, demonstrating high-grade tumor budding (Bd 2/3) and invasion depth of >1,500 um. LNM was significantly correlated with tumor budding (P = 0.030). The overall median follow-up period was 41.00 ± 27.69 months and 33.16 ± 19.05 months in the ESD-alone and ESD + surgery groups, respectively (P = 0.241). Two patients in the ESD group had local recurrence and two patients died. Patients in the ESD + surgery group reported no local recurrence, distant metastasis, or disease-related death. Recurrence (P = 0.074) and survival rates (P = 0.072) were not significantly different between the two groups.

Conclusions: The LNM rate was exceedingly low in patients with T1b. ESD is an effective and safe method for these patients. The necessity of additional surgical treatment after ESD should be comprehensively determined following the patient's characteristics.