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Suppression of immune anti-tumor lymphocytes by macrophages of advanced tumor bearing rats, across a cell impermeable membrane.

In experiments using double and triple chamber cultures it was demonstrated that suppressive macrophages from advanced T8-Guérin tumor (diameter 5--6.5 cm) bearing rats produced a dialysable factor which suppressed the killer activity of lymphocytes from non-advanced T8-Guérin tumor (diameter 0.5--0.7 cm) bearing rats, as well as from nonadvanced h 18R tumor bearing rats and from Ehrlich ascites bearing mice, against T8-Guérin ascitic cells and, respectively, against h 18R ascitic and Ehrlich ascitic cells. The dialysable suppressive factor inhibits immune lymphocytes but has no effect on the lymphotokin itself already produced.

Animals

Pulmonary carcinoma (Jaagsiekte) of sheep. Ultrastructural study of early and advanced tumor lesions.

Lung carcinoma of sheep (Jaagsiekte) is a bronchiolar-alveolar cell carcinoma. Differences in the ultrastructural patterns of early and advanced lesions of the disease are described. A-type and C-type viruses were observed in advanced tumors and were absent in early lesions. Numerous microtubules were characteristic in the epithelial tumor cells of the early lesions and were absent in the advanced tumor. In comparison to the early lesions, extensive cytosome production, surfactant secretion, and glycogen accumulation were observed in the advanced tumor. The immune response to the early tumor lesion was restricted to the peribronchiolar lymph aggregates, while in the advanced stages of the disease the systemic immune response was markedly increased.

Adenocarcinoma, Bronchiolo-Alveolar

[Autologous bone marrow reimplantation in children with advanced tumor. First experiences of feasibility].

In three children with metastatic tumor uncontrollable by conventional chemo- and radiotherapy, bone marrow was obtained under general anesthesia and cryopreserved according to a carefully developed protocol. The autologous bone marrow cells were reinfused after intensive cytostatic therapy and total body irradiation (2 patients). After an aplastic phase of 7--14 days the peripheral blood leukocyte and thrombocyte count began to recover. The toxicity of the intensive treatment preceding the autologous bone marrow transfusion, and the autologous bone marrow cells themselves were well tolerated. The aplastic phase was easily controlled by the use of granulocytes, thrombocytes and erythrocytes. Except for fever and mucosal ulcerations observed during the phase of extreme leukopenia, the general condition of the patients during partial isolation lasting 26--34 days was astonishingly good. One child died 13 weeks after returning home due to a local relapse. The other two patients survived for 6 + and 11 + weeks and are in complete and partial remission respectively. A further evaluation of the clinical significance of autologous bone marrow reimplantations appears to be feasible in pediatric oncology.

Adolescent

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p&#x2009;<&#x2009;0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p&#x2009;=&#x2009;0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p&#x2009;<&#x2009;0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p&#x2009;<&#x2009;0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p&#x2009;=&#x2009;0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans

Multimodal treatment of advanced testicular tumor with radical reductive surgery and multisequential chemotherapy with cis platinum, bleomycin, vinblastine, vincristine and actinomycin D.

Advanced testicular tumors in 34 patients were treated by combination chemotherapy with bleomycin, vinblastine, vincristine, cis platinum and actinomycin D. The therapy was divided into 3 phases: 1) induction, 2) consolidation and 3) maintenance. Induction lasted 4 weeks and consisted of 420 mg. bleomycin, 0.2 mg./kg. vinblastine, 4 mg./kg. cis platinum, and 20 mg. prednisone daily. Consolidation lasted 6 weeks and consisted of 5 mg. actinomycin D, 6 mg. vincristine and 6 mg./kg. cis platinum. Maintenance therapy was achieved with 2.5 mg. actinomycin D every 6 weeks and 1 mg./kg. cis platinum every 3 weeks. A tumor reductive operation was done before induction of chemotherapy in 13 patients and after induction of chemotherapy in 12 patients. Nine patients were treated with chemotherapy alone. Three patients with brain metastases received concomitant radiotherapy to the brain (3,000 rads). A previous operation and chemotherapy had failed in 11 patients and previous radiotherapy had failed in 1 patient. All patients treated had at least 1 objective response (34 of 34 or 100 per cent). Partial clinical remission was achieved in 7 of 34 patients (21 per cent). A complete clinical remission was observed in 27 of 34 patients (79 per cent) and of this group 6 had a relapse. At present, 22 of 34 patients are free of disease from 4 to 24 months, with an average of 13 months (65 per cent). The toxicity consisted of nausea, vomiting, mucositis, alopecia, mild leukopenia and tinnitus. This approach seems to be effective in producing long clinical remissions in the majority of patients with advanced disease.

Adolescent

Phase 1 trial and assay of rubidazone (NSC 164011) in patients with advanced solid tumors.

A new high-pressure liquid chromatographic method was developed for the simultaneous determination of rubidazone and daunorubicin in human plasma at concentrations as low as 60 ng/ml. Clinical toxicity and the stability of rubidazone were studied in nine patients with advanced solid tumors. Rubidazone was administered by i.v. infusion over 1 hr on a single day every 4 weeks. Moderate leukopenia was the dose-limiting toxicity in four of six patients treated at 150 mg sq/m. Assay of rubidazone in plasma samples obtained after administration of rubidazone showed that the drug was stable for at least 7 hr.

Adult

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans

[Experiences with cis-dichlorodiaminoplatinum (II) in the treatment of advanced solid tumors].

Cis-Dichlorodiammineplatinum (II) was administered in 23 patients with far advanced solid malignancies using a dose schedule of 50 mg/m2 every 3 weeks. All patients had previously progressive disease using conventional cytotoxic therapies. More than 50% of the patients had been pretreated with at least 4 different drugs. 9 patients, additionally, had been irradiated. In 4 instances there was objective tumor regression (duration: 1 to 4 months), in 7 patients tumor progression could be stopped for at least one month, 12 patients did not respond. By sufficient fluid administration combined with electrolyte substitution, furosemide and mannitol, no severe toxic side effects could be observed.

Adenocarcinoma

Prognosis and treatment of Wilms' tumor at Great Ormond Street Hospital for Sick Children--1960-1972.

Eighty-one children with a diagnosis of Wilms' tumor who were treated at the Great Ormond Street Hospital for Sick Children between 1960 and 1972 are reviewed. The National Wilms' Tumor Study group staging system is used. Distribution by age and sex in each stage together with survival rate is given. Treatment and prognostic factors are discussed. Wilms' tumor is most common in children below the age of 3 years. There was a survival rate of 87% in Stage I, 36% in Stage II, 8% in Stage III, and 33% in Stage IV. The survival was worse in patients with locally advanced tumor than in patients who had pulmonary metastases in association with a locally resectable tumor. Whole abdominal irradiation is necessary in all patients in whom the tumor has breached the renal capsule. Single agent chemotherapy has not proved effective in preventing relapse in patients with advanced tumors. More intensive therapy is needed in this group to prevent both local recurrence and distant metastases. The addition of multiple drug chemotherapy to nephrectomy and whole abdominal irradiation is already improving the disease-free survival.

Adolescent

[Chemotherapy of skin tumors of the head and neck].

The authors report on the therapeutic results performed in the 126 skin tumors with three different chemotherapic schedules: a) Endovenous Bleomycin (BLM); b) Combined schedule with BLM, Methotrexate (MTX), Cyclophosphamide and Corticoid; c) Local BLM infiltration. There were 42,8 % of complete remission and 87,2 % of responsiveness (effectiveness). The best response rates were achieved in not advanced tumors. Local BLM infiltration has shown the best response rates 63,9 % being this schedule performed mainly in not advanced tumors. Overdosage of local infiltration may produce tissue necrose. Response rates for squamouscell carcinoma and basal cell carcinoma were alike. BMEM therapy presents the best results in the squamous cell carcinoma and the BLM infiltration in the basal cell carcinoma. There were 24 % of recurrence from the complete remissions.

Bleomycin

Dose response in radiotherapy for glottic carcinoma.

All consecutive patients with glottic squamous cell carcinoma treated primarily by radiotherapy from 1965 through 1974 have been analyzed to reveal response of the primary tumor in relation to the dose. This study appears to indicate presence of dose response for all stages of the primary lesions (T) of the glottic carcinoma except for the smallest ones namely TIS, T1a and T1b. The total number of advanced tumors is small and selected. But they tend to indicate presence of dose response. Out of 15 selected patients with T3 and T4 glottic tumors, 5 (33%) had attained local control by primary radiotherapy; two had distant metastasis at onset of therapy, while 5 (33%) needed salvage surgery for control of the residual or recurrent disease. The ultimate success rate is 66% (10 out of 15) for the patients with advanced tumors treated with a conservative approach. An ongoing study indicates similar, if not better preliminary results with high dose radiotherapy.

Adult

A Phase 1 study of high doses of aminopterin with leucovorin rescue in patients with advanced metastatic tumors.

We have conducted a Phase 1 study of aminopterin (AMT) with leucovorin (LV) in 17 patients. AMT was administered by bolus injection every 7 to 14 days in dosages from 25 to 425 mg/sq m. LV rescue was instituted at 24 hr and continued for 48 to 72 hr. At dosages above 50 mg/sq m, we observed nephrotoxicity defined as greater than or equal to a 25% increase in serum creatinine 24 hr after AMT administration, but its incidence was not strictly dose related. Urinary alkalinization and volume expansion appeared to reduce the incidence of nephrotoxicity. Nephrotoxic drug courses were associated with 24-hr plasma AMT levels [3.6 +/- 2.0 (S.D.) X 10(-6) M] which were significantly higher than nonnephrotoxic courses (1.6 +/- 1.0 x 10(-6) M) (p less than 0.05). In nonnephrotoxic courses, serum elimination pharmacokinetics appeared to be biphasic with a t1/2 alpha of 1.08 +/- 0.01 hr and t1/2 beta of 12.31 +/- 0.06 hr. Systemic toxicity (myelosuppression and mucositis) could be prevented in patients with impaired AMT clearance by the administration of LV at an increased dose rate. In several courses, systemic toxicity occurred in spite of apparently normal plasma clearance, suggesting that 24-hr plasma levels may not accurately reflect intracellular drug effects. Cytokinetic studies on bone marrow aspirates allowed determination of the rescue effect of LV and may prove useful in predicting marrow protection.

Aminopterin