scholarly journals Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins

2018 ◽  
Vol 17 (5) ◽  
pp. 539-551 ◽  
Author(s):  
M. S. Eng ◽  
J. Kaur ◽  
L. Prasmickaite ◽  
B. Ø. Engesæter ◽  
A. Weyergang ◽  
...  

Light-controlled immunotargeting of CSPG4+ triple negative breast cancer and malignant melanoma.

2021 ◽  
Vol 8 (27) ◽  
pp. 2439-2443
Author(s):  
Reshma Gopalakrishnan ◽  
Freena Rose ◽  
Jisha Kalathil Thodiyil ◽  
Lovely Jose

BACKGROUND Breast cancer is the most common malignancy in females. Triple negative breast carcinomas (TNBC), one of the molecular subtypes of breast carcinoma, are not sensitive to hormonal therapy and are reported to have aggressive behaviour. The present study was done to evaluate the expression of Ki67 in triple negative breast cancer using immunohistochemistry (IHC) and correlate the Ki67 expression with other clinicopathological variables. METHODS Based on the IHC status (ER, PR, HER neu), 50 triple negative breast carcinoma cases were selected from January 2019 to June 2020 for a cross-sectional study in Department of Pathology, Government medical college Thrissur. Ki67 immunohistochemical staining was done on the tissue sections and the Ki67 score was correlated with clinicopathological variables. RESULTS Of the 50 cases, majority (74 % cases) had high Ki67 expression (score of more than 50 %). High Ki67 score was strongly associated with presence of lymphovascular emboli (LVE) (P value < 0.05). Even though most of the patients were above 50 years (72 %), no significant correlation was seen between age and Ki67 score. The association with tumour size, histopathological type, tumour grade and lymph node status were not statistically significant. CONCLUSIONS Ki67 expression was high in triple negative breast cancer with mean score of 62 %. High Ki67 score correlated with presence of LVE. High Ki67 would predict increased proliferation of breast cancer cells and could be considered as a prognostic marker. KEYWORDS TNBC- Triple Negative Breast Cancer, Ki 67 Score, Clinicopathological Variables


2019 ◽  
Vol 13 ◽  
pp. 117822341983098
Author(s):  
Marcy C Purnell

Introduction: The Bio-Field Array (BFA) is a device that generates a dielectrophoretic electromagnetic field (DEP-EMF) when placed in a hypotonic saline solution and a direct current (dc) of ~3 amperes is applied. Human triple-negative breast cancer (MDA-MB-231 cells) is known to have a high percentage of apoptotic ( P53) deficient cells and some patients can have poor outcomes with current treatments. Objectives: Previously, we reported a strong upregulation of the apoptotic arm of the unfolded protein response, via reverse transcription–quantitative polymerase chain reaction (RT-qPCR), as well as positive annexin staining in this human breast carcinoma, when grown in media prepared with BFA’s dc DEP-EMF treated saline. Here we will examine and discuss cytoskeletal microtubule changes that were noted in the treated breast carcinoma that are strongly suggestive of apoptosis and the possible correlation of these microtubule changes to the upregulation of Junction Mediating and Regulatory Protein ( JMY, a P53/TP53 cofactor) that is known to drive cytoskeleton microfilaments (actin) function. Methods: In addition to microarray and RT-qPCR analyses, we conducted 7 days of fluorescent microscopic analyses of tubulin assays in these treated versus control MDA-MB-231 cells. Results: These data suggest 2 possible forms of apoptosis, rounded and irregular, may be occurring and possibly facilitated by the significant upregulation (via microarray and RT-qPCR) of an important but poorly understood Nucleation-Promoting Factor (NPF), JMY. Conclusions: The ability of the BFA dc DEP-EMF to significantly upregulate JMY and possibly influence the regulation of unbranched (nucleation-microtubule spikes) and branched forms (autophagy) of actin in the cytoplasmic domains may facilitate a “two coffins” or round and irregular necrosis-like apoptosis for this highly aggressive and often apoptotic-deficient breast cancer cell line.


2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 140-140
Author(s):  
Anna Kaminsky

140 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple-negative and neoadjuvant chemotherapy (NAC) is often used in triple-negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive [H score of 10 or less] and HER2 negative or indeterminate [HER2 1+ or 2+ without amplification by FISH]), were identified. Nine of these TNBCs had metaplastic subtype and two groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Average follow-up in MBC group was 43 months and no patients were lost to follow-up. Average tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow-up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%). Follow-up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple-negative paradox is likely not applicable to MBC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1038-1038 ◽  
Author(s):  
Anna Kaminsky ◽  
Rohit Bhargava ◽  
Kandace P McGuire ◽  
Shannon Puhalla

1038 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple negative and neoadjuvant chemotherapy (NAC) is often used in triple negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive (H score of 10 or less) and HER2 negative or indeterminate (HER2 1+ or 2+ without amplification by FISH)), were identified. Nine of these TNBCs had metaplastic subtype and 2 groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Mean follow up in MBC group was 43 months and no patients were lost to follow up. Mean tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple negative paradox is likely not applicable to MBC.


2018 ◽  
Vol 188 (10) ◽  
pp. 2378-2391 ◽  
Author(s):  
Pierre Romero ◽  
Vanessa Benhamo ◽  
Gabrielle Deniziaut ◽  
Laetitia Fuhrmann ◽  
Frédérique Berger ◽  
...  

Medicine ◽  
2015 ◽  
Vol 94 (52) ◽  
pp. e2341 ◽  
Author(s):  
Adnan Aydiner ◽  
Fatma Sen ◽  
Makbule Tambas ◽  
Rumeysa Ciftci ◽  
Yesim Eralp ◽  
...  

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