scholarly journals Dormancy of growth-stunted malignant melanoma: sustainable and smoldering patterns

2014 ◽  
Author(s):  
Claudine Piérard-Franchimont ◽  
Trinh Hermanns-Lê ◽  
Philippe Delvenne ◽  
Gérald E. Piérard
Keyword(s):  
Malignant Melanoma ◽  
Cancer Progression ◽  
Immune Surveillance ◽  
Lymph Node Involvement ◽  
The Body ◽  
Node Involvement ◽  
Visceral Metastases ◽  
Disease Free ◽  
Stimulation Of

The presentations of primary and metastatic cutaneous malignant melanoma (CMM) are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the socalled CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocytemediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear.

Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta
Keyword(s):  
Cancer Therapy ◽  
Dna Synthesis ◽  
Cancer Progression ◽  
Sirna Delivery ◽  
Predictive Marker ◽  
The Body ◽  
Tumor Site ◽  
Target Delivery ◽  
Target Effect

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

scholarly journals Gastrocolic Fistula: A Rare Presentation of Colon Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Chukwunonso Chime ◽  
Madhavi Ravi ◽  
Myrta Daniel ◽  
Harish Patel ◽  
Bhavna Balar
Keyword(s):  
Colon Cancer ◽  
Late Complication ◽  
Survival Rates ◽  
Standard Of Care ◽  
Lymph Node Involvement ◽  
En Bloc ◽  
Rare Presentation ◽  
Additional Advantage ◽  
Node Involvement

Gastrocolic fistulae have been described for benign conditions including penetrating peptic ulcer and complicated pancreatitis. Malignant etiology can arise from gastric or colon cancer and is a rare and late complication with an incidence of 0.3-0.4%. Usual presentation is the classic triad of weight loss, diarrhea, and feculent vomiting. Barium enema has been shown to have the highest diagnostic accuracy but endoscopy offers additional advantage of biopsy to aid in diagnosis of malignant etiology; the role of computed tomography (CT) scan is controversial. Treatment by one-stage en bloc surgical approach is the current acceptable standard of care with variable recurrence and survival rates. Adjuvant chemotherapy would be based on lymph node involvement and patient discussion.

scholarly journals Serum cyfra21-1 associated with biological aggressiveness and poor prognosis in male patients with urothelial carcinoma of bladder.

2020 ◽  
Author(s):  
Haitao Liang ◽  
Yunlin Ye ◽  
Zhu Lin ◽  
Zikun Ma ◽  
Lei Tan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymphovascular Invasion ◽  
Disease Free Survival ◽  
Lymph Node Involvement ◽  
Free Survival ◽  
Node Involvement ◽  
Male Patients ◽  
Disease Free ◽  
Urothelial Carcinoma Of Bladder

Abstract Background : To assess the prognostic value of preoperative serum cyfra21-1 in male patients with urothelial carcinoma of bladder treated with radical cystectomy.Methods: Patients underwent radical cystectomy from 2009-2018 at our center were retrospectively analyzed and 267 male patients met our criterions. The median follow-up was 34 months. The serum level of cyfra21-1 was measured using enzyme linked immunosorbent assay. Patients were divided into two groups (cyfra21-1≤3.30ng/ml and cyfra21-1>3.30 ng/ml). Clinical significance of cyfra21-1 level was assessed.Results: Of the 267 patients, 110 (41.2%) had normal cyfra21-1, while 157 (58.8%) had elevated serum cyfra21-1. The prevalence of lymph node involvement, locally advanced stage (≥ pT3), tumor stages, tumor size and papillary were significantly higher in patients with elevated cyfra21-1 than in those with normal cyfra21-1. Patients with high cyfra21-1 showed worse Disease free survival and Overall survival than those with low cyfra21-1 ( P = 0.001 and 0.007, respectively). In multivariate analysis, High cyfra21-1, lymph node involvement, lymphovascular invasion and papillary were independent predictors of worse Disease free survival ( P = 0.036, <0.001, 0.002, 0.014 respectively). High cyfra21-1, lymph node involvement and lymphovascular invasion were also confirmed as independent predictors of worse Overall survival ( P = 0.038, 0.010, 0.005, respectively.)Conclusions: Elevated cyfra21-1 was associated with greater biological aggressiveness and worse prognosis than normal cyfra21-1.

Sex, Work, and the Victorians

2020 ◽  
pp. 61-80
Author(s):  
Nicola J. Smith
Keyword(s):  
Sex Work ◽  
Body Politic ◽  
The Body ◽  
Sexual Deviance ◽  
Commercial Sex ◽  
Victorian England ◽  
Capitalist Development ◽  
The Public ◽  
Stimulation Of

Focusing on Victorian England, this chapter examines how sex was increasingly constructed as something that was primarily biological in nature, and how this was bound up with discourses of prostitution as a threat to the reproduction of the body politic. In the first section, the author considers how the pathologization of commercial sex as abnormal and unhealthy worked to naturalize the public/private split on which capitalist development rested. In the second section, the author connects the medical, moral, and juridical regulation of sex work to the suppression and stimulation of other modes of sexual deviance including homosexuality. In the final section, the author explores the role of race and empire in constituting white, bourgeois sexuality as natural, privileged, and the antithesis of commercialized sex.

No relationship is indicated between FHIT expression and clinicopathologic prognostic parameters in early stage cervical carcinoma

2003 ◽  
Vol 13 (2) ◽  
pp. 192-196
Author(s):  
C. Baykal ◽  
A. Ayhan ◽  
A. Al ◽  
K. YÜCE ◽  
A. Ayhan
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Lymph Node Involvement ◽  
Depth Of Invasion ◽  
Prognostic Parameters ◽  
Node Involvement ◽  
Disease Free

In this study we investigated FHIT (Fragile Histidine Triad) protein alterations in cervical carcinomas to assess the relation of this gene with cervical cancer. Eighty-eight patients with surgically treated FIGO (International Federation of Gynecology and Obstetrics) stage IB carcinomas of the cervix were included in this study. Clinicopathologic prognostic factors were compared with FHIT expression status. Disease-free and overall survival was evaluated according to prognostic factors and FHIT expression. The FHIT gene was found to be depressed in 53% (47/88) of the tumors. None of the clinicopathologic prognostic parameters showed a correlation with FHIT expression. Univariate survival analysis with the Kaplan-Meier method showed that only the age of the patient is significantly correlated with disease-free survival. Interestingly, when the same analysis was done for 5-year overall survival; diameter of the primary tumor, depth of invasion, occurrence of lymph node involvement, and number of metastatic lymph nodes were found to be statistically significant. Furthermore, multivariate analysis with Cox regression revealed that lymph node involvement was the only independent variable for 5-year overall survival. In the present study there was no statistical correlation between FHIT expression and clinicopathologic prognostic factors or survival figures of the patients. These findings may be explained with the carcinogenic role of FHIT in tumoral progression but not in the tumoral development that takes place after the carcinogenetic period.

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

An Analysis of 800 Breast Cancer Patients Relapsed after Radical Mastectomy

1976 ◽  
Vol 62 (1) ◽  
pp. 99-112 ◽  
Author(s):  
Sergio Di Pietro ◽  
Lucio Bertario ◽  
Giulio Cantù ◽  
Alberto Re
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Survival Rate ◽  
Soft Tissues ◽  
Regional Lymph Node ◽  
Radical Mastectomy ◽  
Lymph Node Involvement ◽  
Free Interval ◽  
Node Involvement ◽  
Visceral Metastases

The chronology of first recurrences, their topographic distribution and survival from mastectomy were retrospectively studied in a series of 800 mastectomized women with special reference to the relationship between these data and treatment delay, T N categories and free interval. Visceral metastases were more frequent in patients under 50 years, whereas local recurrences were more common in patients over 50. The average free interval was 26 months (over 5 years in 18% of cases) and seemed to be influenced little by the treament delay or by tumor size; it was shorter in patients under 50 years and shorter still in patients with lymph node involvement at operation. A similar correlation exists between these parameters and survival. The 5 year survival rate of the 800 cases with recurrence was 52%, which is quite different from the rate generally indicated for surgical cases, and much higher than the rate for the natural history of untreated breast cancer. The survival rate in cases with first metastases confined to the soft tissues is much higher than in those with bone and/or with visceral metastases. The survival after recurrence proves to be significantly influenced by the length of the free interval, but much more by the presence or absence of regional lymph node involvement, so that the lymph nodes status (N–- or N+) turns out to be a prognostic item of primary importance, even after the onset of recurrence.

Correlation of BMI with tumor stage in early breast cancer patients (pts): Pooled analysis of the German SUCCESS A, B, and C trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1602-1602
Author(s):  
Carola Anna Melcher ◽  
Uta Ortmann ◽  
Christoph Scholz ◽  
Thomas Zwingers ◽  
Andreas Schneeweiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Early Breast Cancer ◽  
Primary Breast Cancer ◽  
Tumor Stage ◽  
Lymph Node Involvement ◽  
Phase Iii ◽  
Tumor Characteristics ◽  
Node Involvement ◽  
Disease Free

1602 Background: Independent from known prognostic factors, e.g., tumor size and nodal status, obesity is a risk factor for poor disease free, distant disease free, and overall survival in breast cancer. The aim of this analysis was to examine the correlation of the body mass index (BMI) with tumor characteristics in early breast cancer. Methods: We analyzed the data of 7,997 pts with early, node positive or high risk node negative primary breast cancer treated with adjuvant taxan-based chemotherapy within the German multicenter phase III SUCCESS A, B, or C trials. The pts’ tumor stage at primary diagnosis was classified according to the UICC tumor-node-metastasis (TNM) classification. Additionally, the tumor’s hormone-receptor status and HER2/neu status were determined. Before enrollment into the study each patient was grouped according to the WHO global database on BMI. Contingency table methods were used to analyze the correlation of BMI and tumor characteristics. Results: Among the 7,997 pts 100 (1.3%) pts were underweight, 3,556 (44.5%) pts were normal weight, 2,569 (32.1%) pts were overweight and 1,772 (22.2%) were obese. Of all pts 4,508 pts (56.4%) suffered from a pT2-4 tumor, 4830 (60.4%) showed lymph node involvement (pN1-3) and 7509 (93.9%) had G2-3 tumors. 5839 pts (73.0%) showed positivity for ER or PR and 935 (11.7%) for HER2/neu. Overweight and obese pts had significantly larger tumors compared to pts with normal BMI (p<0.0001; p<0.0001). Furthermore, overweight and obesity were associated with a significantly higher rate of lymph node involvement (p=0.0001; p=0.0003) respectively. In contrast neither grading, tumor histology, ER/PR-status nor HER2/neu-overexpression were correlated with BMI. Conclusions: These data are the first to show in a large number of pts that both obese and overweight women suffering from primary breast cancer have significantly larger tumors and more often positive axillary lymph nodes. As there are no differences in tumor biology, the advanced tumor stage might be due to more difficult and delayed detection of breast cancer and lymph node lesions in these women.

Ugly is not only skin deep: A case of osteogenic melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20009-e20009
Author(s):  
Joshua C.M. Williams ◽  
Natale Tate Sheehan ◽  
Pierre DeDelva ◽  
Jennifer Barr
Keyword(s):  
Lymph Node ◽  
Malignant Melanoma ◽  
Lymph Node Dissection ◽  
Lower Lobe ◽  
Lymph Node Involvement ◽  
Node Dissection ◽  
Inguinal Lymph Node Dissection ◽  
Left Lower Extremity ◽  
Node Involvement ◽  
Initial Biopsy

e20009 Background: Although the incidence of malignant melanoma is high, the incidence of metaplastic malignant melanoma is low. Within the various subtypes of malignant metaplastic melanoma, the manifestation of osteogenic melanoma remains a rarer event. Current review of the literature reveals only 12 reported cases. Of these reported cases, scant discussion is made on treatment whereas the histopathology is discussed in great detail. Methods: We present the case of a 64 year old Caucasian man that was diagnosed with synchronous tumors of the foot and lung. Initial biopsy of the foot revealed metastatic osteogenic melanoma. As a result of the initial biopsy results and imaging, the patient underwent a right lower lobe resection and lymph node dissection followed by a left lower extremity Pirigoff’s amputation and inguinal lymph node dissection. Results: Immunohistochemical staining of the extirpated tissue from the lung revealed strong reactivity to S100, vimentin, Sox10, diffuse reactivity to low molecular weight cytokeratin and HMB-45/MART-1 and no lymph node involvement. Whereas the IHC of the extirpated tissue of the left foot remained consistent with the initial biopsy of strong reactivity to S100 and MART-1 and negative to pancytokeratins, CD34, Desmin, and SMA. Conclusions: Given the features of the patient’s pathology and resected metastatic disease, he was administered adjuvant alpha interferon therapy.

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