Molecular and clinical oncology最新文献

Immunotherapy has emerged as a crucial treatment option, particularly for types of cancer that display resistance to conventional therapies. A remarkable breakthrough in this field is the development of chimeric antigen receptor (CAR) T cell therapy. CAR T cells are generated by engineering the T cells of a patient to express receptors that can recognize specific tumor antigens. This groundbreaking approach has demonstrated impressive outcomes in hematologic malignancies, including diffuse large B cell lymphoma, B cell acute lymphoblastic leukemia and multiple myeloma. Despite these significant successes, CAR T cell therapy has encountered challenges in its application against solid tumors, leading to limited success in these cases. Consequently, researchers are actively exploring novel strategies to enhance the efficacy of CAR T cells. The focus lies on augmenting CAR T cell trafficking to tumors while preventing the development of CAR T cell exhaustion and dysfunction. The present review aimed to provide a comprehensive analysis of the achievements and limitations of CAR T cell therapy in the context of cancer treatment. By understanding both the successes and hurdles, further advancements in this promising area of research can be developed. Overall, immunotherapy, particularly CAR T cell therapy, has opened up novel possibilities for cancer treatment, offering hope to patients with previously untreatable malignancies. However, to fully realize its potential, ongoing research and innovative strategies are essential in overcoming the challenges posed by solid tumors and maximizing CAR T cell efficacy in clinical settings.

The present study evaluated serum levels of vascular endothelial growth factor (VEGF) as a predictor of recurrence in patients with advanced-stage esophageal squamous cell carcinoma (ESCC) following curative esophagectomy followed by chemotherapy or concurrent radiotherapy. Patients with locally advanced resectable ESCC underwent R0 esophagectomy followed by chemotherapy or concurrent radiotherapy as an adjuvant. Serum VEGF levels in 173 patients, including 57 patients with recurrent disease, and 183 healthy controls were determined using a Luminex assay. The results demonstrated that the serum VEGF levels were significantly higher in 57 patients with locally advanced resectable ESCC at recurrence compared with the levels at pre-treatment (P<0.001). The patients with recurrence exhibited significantly higher serum VEGF levels during chemotherapy or concurrent radiotherapy than patients with no recurrence (P<0.05). Patients with low serum VEGF levels had a significantly longer survival time than those with high serum VEGF levels prior to treatment (P<0.01). The median survival times were 70 and 25 months in patients with locally advanced resectable ESCC with serum VEGF levels <161.75 and ≥161.75 pg/ml following treatment, respectively (P<0.01). Compared with patients with VEGF levels <147 pg/ml following treatment, patients with locally advanced resectable ESCC with VEGF levels ≥147 pg/ml had a significantly higher risk of recurrence (P<0.01). Patients with low serum VEGF levels (<147 pg/ml) had significantly higher recurrence-free survival rates than those with high serum VEGF levels (≥147 pg/ml) following treatment (P<0.01). The findings of the present study demonstrate that serum VEGF levels are a potential predictor of recurrence and of the treatment outcomes of chemotherapy or concurrent radiotherapy in patients with locally advanced resectable ESCC.

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are one of the most common types of NETs, accounting for 65-75% of all NETs. However, epidemiological characteristics of patients with GEP-NETs in China are still lacking. The present retrospective study aimed to investigate the local epidemiology of GEP-NETs and assess the prognostic factors in China. The data of 267 patients with GEP-NETs who were admitted to the First Affiliated Hospital of Bengbu Medical College (Bengbu, China) and the Affiliated Hospital of West Anhui Health Vocational College (Lu'an, China) were retrospectively reviewed. The clinical and pathological characteristics of the patients, as well as follow-up information, were collected, and the 5-year survival rate was calculated. Kaplan-Meier curves and log-rank analysis were used to analyze the prognostic factors. The stomach (100/267; 37.5%) was the most common site of GEP-NETs and the liver (25/39; 64.1%) was the most common metastatic site. A total of 166 (62.2%) and 219 (82.0%) patients had positive results for chromogranin A (CgA) and synaptophysin (Syn), respectively. The percentage of patients with tumor grade G1, G2 and G3 was 33.3, 21.0 and 45.7%, respectively. The 5-year overall survival rate was 79.7%, and the age, tumor site, distant metastasis and tumor grading upon diagnosis were all prognostic factors. In conclusion, the present case series investigated the epidemiology and prognostic factors of GEP-NETs in China. CgA and Syn could be used as diagnostic markers for NETs and the stomach was the most common primary tumor site. Lymph node metastasis, tumor site, distant metastasis and tumor grading were important prognostic factors.

Aggressive fibromatosis is a rare clonal proliferative tumor arising from mesenchymal cells in the fascia and musculoaponeurotic structures. The aim of the present study was to describe several cases of extra-abdominal recurrent aggressive fibromatosis. The present study was a single-center retrospective case series of patients with recurrent aggressive fibromatosis. The cases were managed at a single private facility. A total of 9 patients with recurrent fibromatosis were included. The mean and median ages of the patients were 29 and 30 years, respectively. In total, two thirds (66.67%) of the cases were female. A negative previous medical history was reported in 7 cases (77.7%), and diabetes and hypertension were reported in 1 case (11.1%). Overall, only 1 case (11.1%) had a family history of breast fibromatosis. The time interval between primary tumor resection and recurrent presentation was 28 months. In 6 cases (66.7%), the tumor was located in the extremities. Pain was the most common presenting symptom in 6 cases (66.7%). All patients had their recurring tumor surgically removed, followed by radiation in 5 cases. The resection margin was positive in 4 cases (44.4%). Each patient was subjected to a careful three-month follow-up for recurrences. On the whole, the present study demonstrates that despite the fact that several therapeutic approaches for extra-abdominal recurrent aggressive fibromatosis have been described in the literature, there is a significant likelihood of recurrence following resection.

Renal cell carcinoma (RCC) is a heterogeneous and complex disease with numerous pathophysiologic variants. ~40% of patients succumb due to the progression of the disease, making RCC the most fatal of the common urologic malignancies. Prognostic factors are indicators of the progression of the disease, and the precise determination of these factors is important for evaluating and managing RCC. In the present study, it was aimed to determine and find associations among the histopathological features of RCCs and their impact on survival and metastasis. This is a cross-sectional study of RCC cases who have undergone partial or radical nephrectomy from March 2008 to October 2021 and have been pathologically reviewed at Shorsh General Teaching Hospital in Sulaimani, Iraq. The data in the pathology studies were supplemented by follow-up of the patients to obtain information about survival, recurrence and metastasis. In total, 228 cases of RCC were identified, among whom 60.5% were men and 39.5% were women, with a median age of 51 years. The main tumor types were clear cell RCC (71.1%), papillary RCC (13.6%), and chromophobe RCC (11%). Various measures of aggressiveness, including tumor necrosis, sarcomatoid change, microvascular invasion, and parameters of invasiveness (invasion of the renal sinus and other structures), were significantly correlated with each other, and they were also associated with reduced overall survival and an increased risk of metastasis on univariate analysis. However, on multivariate analysis, only tumor size and grade, and microvascular invasion retained statistical significance and were associated with a lower survival rate. In conclusion, pathological parameters have an impact on prognosis in RCC. The most consistent prognostic factors can be tumor size and grade, and microvascular invasion.

Chronic myeloproliferative neoplasms (MPN) include polycythemia vera (PV), primary myelofibrosis, essential thrombocythemia (ET) and chronic myeloid leukemia (CML). Overlapping MPNs are rare; however, they can occur in the same individual. The present case report describes a patient with both triple-negative ET and CML. A 64-year-old woman was followed-up at our hematology clinic at Feist Weiller Cancer Center, Louisiana State University Health Shreveport (Shreveport, LA, USA) since 2000 after she was diagnosed with JAK2V617F-negative ET. The patient remained stable on hydroxyurea until 2012, when they underwent a bone marrow biopsy for progressively increasing white blood cell counts, and the pathology was consistent with CML; PCR for BCR-ABL was positive for both P210 and P190 transcripts. The patient was then initiated on dasatinib. After dasatinib, they were given a trial of imatinib, and were later transitioned to nilotinib and finally to bosutinib (2019) due to unchanged thrombocytosis. Next-generation sequencing from a bone marrow biopsy in 2019 demonstrated an EZH2 mutation that may be associated with triple-negative ET. CML was in major molecular response at that time. The patient was continued on bosutinib with hydroxyurea, after which hydroxyurea was changed to anagrelide due to worsening anemia and persistent thrombocytosis. However, bosutinib and anagrelide were discontinued due to worsening pulmonary hypertension. The patient was noted to have peripheral blasts of 14% by flow cytometry, after which they underwent a repeat bone marrow biopsy in 2022, which showed extensive myelofibrosis. BCR-ABL transcripts were undetectable. Given their accelerated myelofibrosis, the patient was started on a hypomethylating agent, decitabine/cedazuridine, along with darbepoetin for anemia in June 2022. Given their persistent thrombocytosis, the patient was also started on peginterferon α. Most studies reporting two clonal processes in the same patient have been for PV and CML. To the best of our knowledge, this is the first reported case of triple-negative ET with double transcript CML in the same individual.

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

A 60-year-old male patient underwent laparoscopic radical cystectomy with bilateral pelvic lymph node dissection and urinary diversion as a treatment for muscle-invasive bladder cancer and was discharged two weeks later. One month later, the patient was readmitted with septic and haemorrhagic shock, and was diagnosed with right external iliac artery disruption. The patient underwent an exploratory operation and a vessel split of the right external iliac artery was found. The artery split was covered by a vascular stent. Klebsiella pneumoniae subsp. Pneumoniae was isolated in blood culture and the patient then received adequate antibiotics based on the drug sensitivity test. The patient eventually had a good recovery and was discharged five weeks later. In summary, although iliac artery injury after successful pelvic surgery is a rare event, this life-threatening complication should be taken into full consideration, particularly in patients with high-risk factors such as diabetes mellitus.

Glioblastoma multiforme (GBM) is the most frequent and malignant primary central nervous system tumor in adults. The gold-standard management of GBM includes post-operative radiotherapy (RT) with concurrent and secondary temozolomide (TMZ) treatment. The present meta-analysis study examined the efficacy of the early administration of bevacizumab prior to standard RT plus TMZ in managing patients with GBM and unfavorable prognostic factors. Between 1983 and 2020, the present study looked for comparative articles involving standard RT plus TMZ and RT/TMZ combined with bevacizumab treatment in patients with GBM. The primary outcomes involved in this study include progression-free survival and overall survival. The present study suggested that bevacizumab administration plus standard RT/TMZ (BEV group) treatment was associated with increased survival of patients with GBM compared with those treated with standard RT/TMZ (CG/Control group) treatment only.

The translationally controlled tumor protein (TCTP) is a highly conserved protein involved in a variety of normal cell functions and disease processes. Preclinical studies revealed that TCTP has anti-apoptotic properties, promotes cell growth and division and is involved in cancer progression by promoting invasion and metastasis. The present study explored the potential value of TCTP as a prognostic marker in colon cancer. A retrospective analysis of 74 patients with colon cancer was performed. Using immunohistochemistry, TCTP levels in the primary tumor were assessed semi-quantitatively by the calculation of cytoplasmic and nuclear H-score. Cytoplasmic TCTP levels in the primary tumor had no statistically significant association with disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) in the present patient population. Patients whose primary tumors had a negative nuclear TCTP expression had significantly improved clinical outcomes. The PFS for the negative nuclear TCTP expression group was 7.7 months [95% confidence interval (CI), 5.8-9.5] compared with 5.5 months (95% CI, 3.2-7.8) in the group with positive nuclear expression (P=0.023, Mantel-Cox log-rank). Patients with a negative nuclear expression of TCTP had a significantly higher median OS (22.2 months; 95% CI, 16.1-28.3) compared with those with positive TCTP nuclear expression (median 13.2 months; 95% CI, 10.1-16.3; P=0.008, Mantel-Cox log-rank). In a multivariate Cox regression model, a positive nuclear TCTP H-score was an independent risk factor for worse PFS and OS. The 1-year OS rate in the group with negative nuclear TCTP expression was 86.3% compared with 56.5% in patients with positive nuclear TCTP expression (P=0.008). The present study suggested that semiquantitative H-score measurement of TCTP levels in the nuclei of tumor cells from the primary tumor is a potential prognostic marker for clinical outcomes in patients with colon cancer.