scholarly journals The Role of BiP and the IRE1α–XBP1 Axis in Rhabdomyosarcoma Pathology

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4927
Author(s):  
Mahmoud Aghaei ◽  
Ahmad Nasimian ◽  
Marveh Rahmati ◽  
Philip Kawalec ◽  
Filip Machaj ◽  
...  

Background: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, and is associated with a poor prognosis in patients presenting with recurrent or metastatic disease. The unfolded protein response (UPR) plays pivotal roles in tumor development and resistance to therapy, including RMS. Methods: In this study, we used immunohistochemistry and a tissue microarray (TMA) on human RMS and normal skeletal muscle to evaluate the expression of key UPR proteins (GRP78/BiP, IRE1α and cytosolic/nuclear XBP1 (spliced XBP1-sXBP1)) in the four main RMS subtypes: alveolar (ARMS), embryonal (ERMS), pleomorphic (PRMS) and sclerosing/spindle cell (SRMS) RMS. We also investigated the correlation of these proteins with the risk of RMS and several clinicopathological indices, such as lymph node involvement, distant metastasis, tumor stage and tumor scores. Results: Our results revealed that the expression of BiP, sXBP1, and IRE1α, but not cytosolic XBP1, are significantly associated with RMS (BiP and sXBP1 p-value = 0.0001, IRE1 p-value = 0.001) in all of the studied types of RMS tumors (n = 192) compared to normal skeletal muscle tissues (n = 16). In addition, significant correlations of BiP with the lymph node score (p = 0.05), and of IRE1α (p value = 0.004), cytosolic XBP1 (p = 0.001) and sXBP1 (p value = 0.001) with the stage score were observed. At the subtype level, BiP and sXBP1 expression were significantly associated with all subtypes of RMS, whereas IRE1α was associated with ARMS, PRMS and ERMS, and cytosolic XBP1 expression was associated with ARMS and SRMS. Importantly, the expression levels of IRE1α and sXBP1 were more pronounced in ARMS than in any of the other subtypes. The results also showed correlations of BiP with the lymph node score in ARMS (p value = 0.05), and of sXBP1 with the tumor score in PRMS (p value = 0.002). Conclusions: In summary, this study demonstrates that the overall UPR is upregulated and, more specifically, that the IRE1/sXBP1 axis is active in RMS. The subtype and stage-specific dependency on the UPR machinery in RMS may open new avenues for the development of novel targeted therapeutic strategies and the identification of specific tumor markers in this rare but deadly childhood and young-adult disease.

2020 ◽  
Vol 22 (1) ◽  
pp. 43-46
Author(s):  
Mst Jesmen Nahar ◽  
Md Mahiuddin Matubber ◽  
Md Mahbubur Rahman ◽  
Md Mahbubur Rahman ◽  
Syed Muhammad Baqul Billah ◽  
...  

Background: Carcinoma stomach, a major killer cancer all over the world, is still presenting late in developing countries due to delay in early diagnosis, lack of awareness, infrastructure etc. Objectives: To establish the importance of preoperative evaluation on operability of carcinoma stomach. Methods: Sixty clinically and histopathologically diagnosed ca stomach cases who underwent surgery in department of Bangabandhu Sheikh Mujib Medical University, Dhaka, and Dhaka Medical College Hospital, Dhaka in 2011 were assessed with clinical picture, investigations, preoperative evaluation and peroperative findings were recorded. Z test for proportion was used to assess clinical decision predictability with a p value of :s;0.05 as significant. Results: Male (73.33%) predominant with 2.75:1 male:female ratio was observed. Mobility, fixity and abdominal lymphadenopathy were not well detected through clinical assessment (p=0.001) while ascites, metastasis and Shelf of Slummer were similar in both clinical and operative finding. The endoscopy of upper GIT finding gave a unique picture as the findings were almost same as were found during operation. USG detected a lesser proportion of the clinical condition compared to peroperative condition whereas CT performed better than the USG except for the lesion detection. Though Computed Tomography (CT) detected higher percentage of lesion, metastasis, ascites and lymph node involvement compared to ultrasonogram (USG), it was significantly higher only for lesion detection (p=0.002) and lymph node involvement (p=<0.001). In the similar manner USG assessment of lesion detection (p=<0.001) and lymph node involvement (p=0.003) was significantly low compared to operative finding. When we looked between CT and operative finding only lesion detection was significantly low (p=0.01) indicating CT to be most effective predictor of clinical picture for operative decision. Preoperative plan were mostly not in accordance with peroperative decision except for total gastrectomy. Conclusion: The study indicates weakness in clinical detection and pre-operative plan compared to per-operative finding. Hence combination of clinical feature and investigation tools especially endoscopy of upper GIT combined with CT is recommended to predict a better operative decision. Journal of Surgical Sciences (2018) Vol. 22 (1): 43-46


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1602-1602
Author(s):  
Carola Anna Melcher ◽  
Uta Ortmann ◽  
Christoph Scholz ◽  
Thomas Zwingers ◽  
Andreas Schneeweiss ◽  
...  

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.


1989 ◽  
Vol 75 (5) ◽  
pp. 494-497 ◽  
Author(s):  
Giovanni Battista Secco ◽  
Roberto Fardelli ◽  
Elisabetta Campora ◽  
Salvatore Rovida ◽  
Gabriella Lapertosa ◽  
...  

Two hundred and nine cases of primary gastric cancer were treated surgically from January 1968 to December 1983 and analyzed retrospectively. All patients were followed up for a minimum of 5 years. There were 25 SI cases (12 %), 22 SII (10.5%), 55 SIII (26.3%) and 107 SIV (51.2%). Tumor grade according to Broders classification showed 50 cases of G1 lesions (23.9%), 44 G2 (21.1 %) and 115 G3 (55%). Patients with well differentiated G1 lesion, compared to G2-G3 patients, presented a greater incidence of T1-T2 tumors and decreased incidence of T4 tumors (p < 0.05). The lymph node involvement rate significantly increased with variation of T (p < 0.001) but not with tumor grade. Survival results correlated with tumor stage (p < 0.01) but not with tumor grade or histological type.


2019 ◽  
Vol 58 (02) ◽  
pp. 86-92 ◽  
Author(s):  
Jamshid Farahati ◽  
Uwe Mäder ◽  
Elena Gilman ◽  
Rainer Görges ◽  
Ines Maric ◽  
...  

Abstract Aim to evaluate the time trend of epidemiology of follicular cell derived thyroid cancer (TC) based on data from a well documented cancer registry. Methods Population based data on TC from Lower Franconia (LF), Germany, within 1981 and 2015 were analysed to estimate the regional epidemiology of TC. The incidence was assessed in 5-year-intervals for gender, histology, and tumor stage. Results Incidence of TC solely attributable to papillary TC (PTC) doubled mainly in T1- and T2-stages within the evaluation period from 4.5 to 8.7/100.000/y in females and 1.7 to 4.1/100.000/y in males. There was no significant change of follicular TC (FTC), whereas anaplastic TC (ATC) decreased in the same interval. The number of lymph-node metastases and T3-cases increased, while the frequency of T4-stage and distant metastases decreased. Increased incidences of T1- and T2-stages suggest an over-diagnosis. In contrast, increasing number of tumors at T3-stage and with lymph node involvement contradict the over-diagnosis as the only reason for rising incidence. Declining of T4-stages in spite of increasing of T3-stages and N1-cases indicates the value of timely detection and treatment of TC. In accordance, reduced incidence of advanced cancers with M1-stage and ATC cases promote our current management of TC. Conclusion Timely diagnosis and adequate risk-adopted treatment of thyroid cancer reduce the frequency of high-risk cases with distant metastases and the possible protracted dedifferentiation of TC to anaplastic features. Our analyses support the management algorithm in thyroid cancer according to the recent guidelines of German Nuclear Medicine Society.


2007 ◽  
Vol 73 (7) ◽  
pp. 674-678 ◽  
Author(s):  
Andrew J. Page ◽  
Grant W. Carlson ◽  
Keith A. Delman ◽  
Douglas Murray ◽  
Andrea Hestley ◽  
...  

Completion lymph node dissection (CLND) is routinely performed after metastatic melanoma is detected at sentinel lymph node (SLN) biopsy. Nonsentinel lymph node (NSLN) involvement is found in less than one-third of the cases. Possible predictors of NSLN involvement are examined. A retrospective review of 70 patients with a positive SLN biopsy for melanoma and drainage to one lymphatic basin was performed. The size of metastatic deposits was defined as macrometastases (>2 mm), micrometastases (≤2 mm), a cluster of cells (10–30 grouped cells) in the subcapsular space or interfollicular zone, or isolated melanoma cells (1–20 or more individual cells) in sub-capsular sinuses. Tumor stage, ulceration, SLN tumor burden, mitoses, number of positive SLNs, and total number of lymph nodes removed were examined as predictors of NSLN involvement after CLND. Two additional models based on SLN tumor burden and the number of nodes biopsied were designed. Nineteen patients (24.3%) were found to have NSLN metastases after CLND. Tumor stage, ulceration, SLN tumor burden, mitoses, number of positive SLN, and number of lymph nodes removed were not statistically significant. Residual disease at CLND stratified by SLN tumor burden was: isolated melanoma cells, 0; cluster of cells, 8 (38.1%); ≤2 mm, 5 (20.8%); and >2 mm, 6 (27.3%). A comparison of the means for the models was not predictive of NSLN involvement. None of the risk factors or models examined could predict nonsentinel lymph node involvement with melanoma. The SLN sample and minimal SLN metastatic disease when defined as isolated clusters of cells warrant further study as a potential indicator against CLND after positive SLN.


Author(s):  
El Mahdi Graiouid ◽  
Walid Bai ◽  
Messian Gallouo ◽  
Abderrahmane Doumer ◽  
Mohammed Dakir ◽  
...  

Objectives: For a better staging of bladder tumors, we studied the characteristics and the clinical tumor stage in a series of patients and we compared them with the anatomopathological results of cystectomy. Materials and methods: The clinical data of 126 patients who had had radical cystectomy with ilio-obturator dissection for bladder cancer in our department were analyzed retrospectively. Results: Of the 126 cases studied, 86% were men (109 cases) and 14% women , the average age in our series is 60 years. There was a correlation in 48.4% of the cases. The differences between clinical and pathological stages were statistically significant, the agreement was moderate with a percentage of 1.5% of pT0 at the cystectomy site (P <0.005). We found the following results: 100% of the 2 T0 tumors were T2. 80% of the 31 T1 tumors were T1, while 7 were T2; 28.3% of T2 tumors were T2, 11.6% were superficial tumors; 77.7% of T3 tumors were T3; 100% of T4 tumors were T4. Pathological lymph node involvement was diagnosed in 77 patients (61.1%) while only 19.8% was diagnosed with an abdominopelvic CT scan (P <0.005). Conclusion: This study demonstrated the high risk of the presence of an increase or decrease in the local stage of the primary tumor and of lymph node involvement.


Author(s):  
Narges Zamani ◽  
Mitra Modares Gilani ◽  
Majid Mirmohammadkhani ◽  
Sharzad Sheikhhasani ◽  
Azamsadat Mousavi ◽  
...  

Objectives: Uterine endometrial cancer (EC) is the most common female reproductive system malignancy. There are various comments on pelvic and para-aortic lymphadenectomy during the surgical staging of EC. Several oncologists believe that total lymphadenectomy, in some cases, may lead to operative morbidity without any considerable advantage over more surveillance, especially in patients with comorbidities. The purpose of the current study was to examine the correlation between serum tumor marker levels and stage, grade, histological type, myometrial invasion, and lymph node involvement in EC. Materials and Methods: A total of 131 patients with EC participated in the present cross-sectional study. Preoperative serum CA125 and HE4 levels were evaluated 1 week before surgery. Then, the stage, grade, and lymph node involvement were recorded according to the pathological findings. After Data analysis through SPSS software, P value<0.05 was considered to be significant. Results: One hundred thirty-one patients with EC (70, 31, 15, and 15 patients in sequence with stages IA, IB, II, and III) were analyzed. The serum CA125 and HE4 levels were significantly higher in more advanced stages (over IA), (P=0.016 and P=0.004, respectively). Levels of both tumor markers were significantly higher in patients with lymph node involvement, and cervical and myometrial invasions. In logistic regression analysis, a significant correlation was found between HE4 level (odds ratio [OR]=1.005, P=0.035) and grade of disease (OR=2.137, P=0.005). Conclusions: HE4 and CA125 are useful for predicting high-risk patients. Sensitivity of 64% and specificity of 60% were indicated at cut-off value of 70 pmol/L for HE4 in stage IA in comparison with stages over IA. Although the ideal cut-off which is defined as higher than 80% was not obtained, such a cut-off (60%) can also be considered for preoperative evaluation of surgical staging of EC.


2018 ◽  
Vol 6 (1) ◽  
pp. 257
Author(s):  
Deepak Paul ◽  
Moothedathparambil Ramakrishnan Babu ◽  
Krishnakumar Marar

Background: Involvement of cervical lymph nodes is the single most important prognostic factor in oral carcinoma. This study was aimed to evaluate the correlation between tumour stage and lymph node metastasis.Methods: A descriptive study was planned in oral cancer patients who fall within the inclusion criteria. This was compared with the postoperative histopathologic status of cervical nodes. Correlation analysis was done between tumor stage and lymph node metastasis.Results: Total 106 patients were included in the study. The male female ratio was 1.4:1. Majority of the patients 37(34.9%) were in the sixth decade of life. Carcinoma of the tongue was present in 17 cases while only 4 had carcinoma of lower alveolus. Most of the patients with oral cancer presented at an early stage (T1-T2). Stage IV was the commonest with 51 (48.1%) patients. Level I was the most commonly involved lymph node station (78.1%) in squamous cell carcinoma of oral cavity. A weak significant positive correlation between tumor stage and lymph node metastases (r =0.298) was found (p = 0.002). There was a moderate significant (p = 0.0001) positive correlation (r = 0.435) between pathological tumour stage and level of lymph node involvement. But the positive correlation was not statistically significant in carcinoma of the lower alveolus (r = 0.387, p=0.112).Conclusions: Significant positive correlation between pathological tumor stage and level of lymph node involvement in oral cancer and carcinoma tongue. But, in carcinoma lower alveolus the positive correlation was not significant.


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