Mechanism Of Spontaneous Regression Research Articles

Spontaneous regression of brain tumors in children: case report and literature review

Introduction: They are defined as space-occupying lesions that present radiological characteristics of tumors and that resolve spontaneously during radiological follow-up. Spontaneous regression of tumors is a rare phenomenon, with a regression rate in malignant tumors of 1/60,000 to 100,000 patients. Materials and Methods: An 11-year-old female with polydipsia, polyuria, 5 kg weight loss, ataxia, headache, vision loss, and diabetes insipidus. CT with chiasm-dependent tumor occupying the interpenduncular cistern, displacing the hypothalamus ventrally. Results: An excisional biopsy was performed using a pterional approach, microsurgical resection + ultrasonic aspiration, during the trans-surgical procedure thickening of the chiasm and optic nerves was found. WHO Grade I Pilocytic Astocytoma was reported. In the two-year follow-up with magnetic resonance imaging of the brain, we observed complete tumor regression. Discussion: Partial cytoreduction of the tumor, biopsy, radiotherapy or chemotherapy play a role in the initiation of tumor apoptosis. Surgical trauma favorably alters the biological activity of the tumor and the immunological status of the host. Conclusions: The mechanisms of spontaneous regression and spontaneous involution of residual tumor after surgery are not known. Apoptosis may be the common denominator, possible mechanisms include immunological, genetic and biological factors.

MECHANISMS OF SPONTANEOUS REGRESSION OF MALIGNANT TUMORS IN INFLAMMATION

Annotation: The study of the mechanisms of spontaneous regression of malignant tumors is a topical issue of our century. Disclosure of the pathogenesis of regression will allow progress in the treatment of such diseases. The article discusses the mechanisms of regression of malignant tumors in inflammation, discloses the role of bacteria in this issue, and analyzes the possible mechanism of immunity sensitization in such diseases. The review of immune mechanisms was carried out on the basis of these articles, which studied the Coli toxin, BCG vaccine. The results showed the effectiveness of the use of these funds in the treatment of cancer patients. The possibilities of using bacteria for the transfer of drugs to the tumor area and their production of cytokines are also described. In addition, the correlation between the time of onset of inflammation and regression of tumor formation was analyzed. The main antitumor compounds and substances (IL-1, IL-12, TNF family, LIGHT and CCL21) were also noted, their effect on tumor cells and their role in the regression of malignant tumors was described. As a result, it was concluded that bacteria increase the ability of the immune system to recognize and attack tumor cells, however, the individual characteristics of the reactivity of the human immune system should be taken into account before such therapy.

Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report

BackgroundSpontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood.Case presentationAn 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3.4-cm solid tumor with a heterogeneous irregular center and no fibrous capsule in liver segment 8 (S8). An enhanced computed tomography (CT) scan revealed a tumor in S8 with heterogeneous enhancement in the arterial phase and washed out insufficiently in the portal and equilibrium phase. The enhanced pattern on magnetic resonance imaging was similar to that of CT. Although the imaging findings were not typical for HCC, liver resection (S8) was performed with HCC as the most probable diagnosis. Histopathological examination of the resected specimen showed that the tumor was well to moderately differentiated HCC with unique features. Approximately half of the tumor was composed of well-differentiated HCC that was focally accompanied by dense lymphocyte infiltration. The other half of the tumor was fibrotic tissue that resembled an inflammatory pseudotumor. Several foci of moderately differentiated HCC were scattered within the tumor with a nodule-in-nodule appearance, and the foci totally showed coagulative necrosis. On immunostaining, lymphocytes in the tumor stroma were positive for CD8 and programmed death 1. The expression of programmed death-ligand 1 was observed in carcinoma cells and macrophages specifically within the lymphocyte-rich area of HCC.ConclusionsWe consider this case representative of spontaneous regression of HCC, and the immune response against HCC might contribute to tumor regression, leading to complex histopathological appearances. This case may provide insight into the mechanism of spontaneous regression of HCC.

Identification of LncRNAs as Therapeutic Targets in Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia (CLL) is one kind of blood cancer that has a very heterogeneous biological background, which results in diverse stages of the CLL and complex treatment strategies. However, a small part of the tumor may disappear without receiving any treatment. This condition is known as “spontaneous regression” and occurs as a result of a poorly investigated mechanism. Exposing the underlying causes of this condition can lead to a novel treatment approach for CLL and other types of cancer. While most such mechanisms have been assumed to be directly linked to protein coding genes, a recent approach was aimed to carry out more comprehensive studies by focusing on non-protein coding genes as well as protein-coding genes at the RNA level. In this article, we applied in-silico analysis of total RNA expression data from 24 CLL samples to determine possible regulatory mechanisms of spontaneous regression in CLL. These were selected by comparing spontaneous regression with progressive samples of CLL at the transcriptional level. As a result, 33 lncRNAs were found to be significantly differentially expressed among these conditions based on differential gene expression analysis. Current study suggested lncRNAs, PTPN22-AS1, PCF11-AS1, SYNGAP1-AS1, PRRT3-AS1 and H1FX-AS1 as potential therapeutic targets to trigger spontaneous regression. Eventually, the results presented here reveal new insights into the spontaneous regression and the relation with the non-coding RNAs, particularly lncRNAs.

Resolving mystery behind autonomous retrogression of low-grade gliomas: A systematic review.

To review evidence-based data on spontaneous retrogression of low-grade gliomas with respect to interval till regression, type of glioma and patient outcome. The systematic review comprised medical literature in English language published from January 1997 to January 2017 on Scopus, PubMed and Google Scholar databases to establish consensus about the possible mechanism of spontaneous regression, the role of therapeutic intervention and failure of management strategies in low-grade gliomas. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed during the review. Of the 176 articles identified, 73(41.5%) were shortlisted for detailed assessment. Of them, 10(13.7%) were included; 5(50%) case reports and 5(50%) case series. There were 23 cases of spontaneous regression; 15(65.2%) males and 8(34.7%) females. The interval of regression varied from 3 months to 15.5 years, and the most commonly presenting low-grade glioma type was optic pathway glioma 11(47.4%). The phenomenon of regression was most evident in optic pathway glioma. Literature suggested that low-grade gliomas should undergo serial imaging before implying any therapeutic intervention. However, the evidencebased proof, large-scale experimental studies and ethical considerations are still required to standardise this strategy.

Spontaneous regression of hepatocellular carcinoma: A mini-review.

Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma (HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively among the 15 cases for which the information regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report

Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms.

Enumeration of leukocyte infiltration in solid tumors by confocal laser scanning microscopy

BackgroundLeukocytes commonly infiltrate solid tumors, and have been implicated in the mechanism of spontaneous regression in some cancers. Conventional techniques for the quantitative estimation of leukocyte infiltrates in tumors rely on light microscopy of immunostained thin tissue sections, in which an arbitrary assessment (based on low, medium or high levels of infiltration) of antigen density is made by the pathologist. These estimates are relatively subjective and often require the opinion of a second pathologist. In addition, since thin tissue sections are cut, no data regarding the three-dimensional distribution of antigen can be obtained.ResultsTo overcome these problems, we have designed a method to enumerate leukocyte infiltration into tumors, using confocal laser scanning microscopy of fluorescently immunostained leukocytes in thick tissue sections. Using image analysis software, a threshold was applied to eliminate unstained tissue and residual noise. The total antigen volume in the scanned tissue was calculated and divided by the mean cell volume (calculated by "seeding" ten individual cells) to obtain the cell count. Using this method, we compared the calculated leukocyte counts with those obtained manually by ten laboratory personnel. There was no significant difference (P > 0.05) between the cell counts obtained by either method.We then compared leukocyte infiltration into seven tumors and matched non-malignant tissue obtained from the periphery of the resected tissue. There was a significant increase in the infiltration of all leukocyte subsets into the tumors compared to minimal numbers in the non-malignant tissue.ConclusionFrom these results we conclude that this method may be of considerable use for the enumeration of cells in tissues. Furthermore, since it can be performed by laboratory technical staff, less time input is required by the pathologist in assessing the degree of leukocyte infiltration into tumors.

Electron microscopic observation of established chondrocytes derived from human intervertebral disc hernia (KTN-1) and role of macrophages in spontaneous regression of degenerated tissues

Background context: Biological and pathological cell processes during the degeneration of intervertebral discs are as yet poorly understood.Purpose: An electron microscope was used to observe disc hernia degeneration at the cellular level as expressed in extruded tissue from a human intervertebral disc and in cultured chondrocytes. The mechanism of spontaneous regression was analyzed in order to investigate the effects of homologous macrophages, and the results of this analysis may be developed into a clinical therapy.Study design/setting: Extruded tissue specimens excised during surgery on human intervertebral disc hernia and cultured chondrocytes isolated from the excised tissue were observed by means of electron microscopy. Extracellular matrix metalloproteinase-3 (MMP-3) and its antagonist, tissue inhibitor of metalloproteinases-1 (TIMP-1), were observed by means of immune electron microscopy. Macrophages confirmed by CD68 immunostaining were added to the chondrocyte culture and observed by means of electron microscopy.Patient sample: All control subjects and patients gave written consent to the study.Outcome measures: KTN-1 was directly observed without culture, and nuclei degeneration, the development of chromatin granules, changes in the osmotic pressure of the nuclear membrane and rough-surfaced endoplasmic reticulum, and the development of fat droplets were observed.Methods: Tissues excised during surgery were divided, a part of the tissues were fixed in various fixatives for electron microscopy and immune electron microscopy analysis, and the other part was treated with collagenase. In addition, chondrocytes were isolated and cultured. Human peripheral blood mononuclear cells were separated using the Ficoll method. After culturing the cells, macrophages were collected, added to the chondrocyte culture, and observed under an electron microscope. CD68 positivity of the macrophages was confirmed by CD68 immunostaining.Results: Freshly isolated chondrocytes in the hernia's extruded region differed markedly from cultured chondrocytes. By means of immunoelectron microscopy, MMP-3 and TIMP-1 were localized at the endoplasmic reticulum of the cultured chondrocytes. Infiltration of macrophages among the chondrocytes was observed in the mixed culture.Conclusions: The tissue extruded from the intervertebral disc showed obvious signs of degeneration, such as changes in osmotic pressure. Macrophages were observed to be the mechanism of spontaneous regression.

Evidence of apoptosis in neuroblastoma at onset and relapse. An analysis of a large series of tumors.

Neuroblastoma (NB) is a tumor of pediatric age that is associated with high mortality in metastatic stages, although stage IVS patients undergo frequent spontaneous regression. Since apoptosis has been proposed as a possible cause of remission among cancer patients, we tested this hypothesis among both localized and metastatic NB and, in particular, NB metastatic stage IVS. We have assayed 36 localized and 117 metastatic neuroblastomas for evidence of internucleosomal DNA degradation and confirmed DNA fragmentation by the flow cytometric Terminal deoxynucleotidyl Transferase method, which also allowed us to measure DNA content and cell cycle phases. These techniques provided evidence of apoptosis in 18 out of 153 samples (11.8%), that were equally distributed among all stages except IVS, i.e. 11.1% in stage I (2/18), 11.1% in stage II (2/18), 13.2% in stage III (5/38), 13.4% in stage IV (9/67), and 0% in stage IVS (0/12). Tumor tissue samples collected at onset and also at relapse for the same patients showed that apoptosis may occur at relapse. In addition, cells appear to undergo apoptosis independently from N-myc amplification, cell cycle phase and DNA ploidy. In conclusion, apoptosis seems to take place with about an equal frequency for both favourable and unfavourable stages with an exception for IVS. Since DNA fragmentation remained undetected in stage IVS, we suggest that apoptosis is not a mechanism of spontaneous regression for these patients. A better basic understanding of the complex molecular mechanisms and biochemical pathways that control apoptosis in neuroblastoma appears to be necessary.

Spontaneous regression of cancer

Spontaneous regression of cancer is one of the most fascinating phenomena observed in medicine. It is generally regarded as inexplicable, although there are now some laboratory studies of regressed or regressing tumours, as well as new theoretical possibilities about mechanisms. In this review, the historical background, clinical features and possible mechanisms are discussed. The clinical aspects of the malignancies most often reported to undergo spontaneous regression, namely renal cell carcinoma, neuroblastoma, carcinoma of the breast, malignant melanoma and leukaemias/lymphomas, are reviewed. The prevalent view regarding the mechanism for spontaneous regression is the involvement of immunological factors in the host. Other mechanisms include hormonal changes, tumour necrosis, trauma and changes in blood supply. Recent. reports suggest other mechanisms such as apoptosis and differentiation to a benign tumour. Decreased telomerase activity has been reported in neuroblastomas that regress, and hypomethylation of DNA in retinoblastoma is a possibility. A role for cytokines and/or growth factors is also discussed. The significance of spontaneous regression is the demonstration of endogenous control of neoplastic growth. Spontaneous regression of cancer is defined as the complete or partial disappearance of malignant tumour in the absence of therapy that is capable of inducing anti-neoplastic effects. Most patients ultimately relapse, so it is not usually associated with cure of the malignant disease. The existence of spontaneous regression is often questioned; indeed, review of the literature reveals reported cases which do not represent malignant disease, instances in which documentation of metastases is questionable and some reported cases in which therapy may have played a role. In 1966, Everson and Cole published a classic monograph on this topic which included 176 well- documented cases of spontaneous regression of cancer published from 1900 until 1964, and listed criteria for the diagnosis (1). These are: documented histologic regression of biopsy-proven metastases; radiologic regression of

Prenatal carcinogenesis. An Appraisal

Prenatal carcinogenesis. An Appraisal