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1. 1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model

Author

Kayleigh Slater, Rosa Bosch, Kaelin Francis Smith, Chowdhury Arif Jahangir, Sandra Garcia-Mulero, Arman Rahman, Fiona O’Connell, Josep M. Piulats, Valerie O’Neill, Noel Horgan, Sarah E. Coupland, Jacintha O’Sullivan, William M. Gallagher, Alberto Villanueva, and Breandán N. Kennedy

Subjects
cysteinyl leukotriene, uveal melanoma (UM), xenograft model, tumour metabolism, inflammation, immunohistochemistry, Medicine (General), R5-920
Abstract

Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84–1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT1) expression associates with poor outcomes. CysLT1 antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT1 expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08–4.78), solidifying the disease relevance of CysLT1 in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-α. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT1 and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM.

Published
2023
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3. THE MADURA FOOT - A CASE REPORT

Author

Nazimuddin Mohammad, Chowdhury Arif, Parvin Rukhsana, Uddin Rokon, Razzak Abdur, and Hoque Moydul

Subjects
Madura foot, Actinomyces, granules, pathogens, Bangladesh, Dermatology, RL1-803
Abstract

Madura foot or mycetoma is a chronic granulomatous disease characterized by localized infection of subcutaneous tissues by actinomycetes or fungi. The inflammatory response can extend to the underlying bone. Mycetoma was described first in the mid 1800s and was initially called Madura foot. The infection can be caused by true fungi (eumycetoma) in 40%, or filamentous bacteria (actinomycetoma) in 60%.Actinomycetoma may be due to Actinomadura madurae, Actinomadura pelletieri, Streptomyces somaliensis, Nocardia species. The infection, which may remain latent for a time, forms small, subcutaneous swellings that enlarge, soften with pus, and break through the skin surface, with concurrent invasion of deeper tissues. Sulfonamide, iodide, and antibiotic therapy have been used against actinomycotic infections, but the fungi are more resistant to treatment. We reported a patient of madura foot from International Medical College Hospital, Tongi, Gazipur. A 82-years old male was admitted to the International medical college hospital with a 16 months history of swelling with multiple discharging sinuses filled with granules localized in his right foot. Pus was examined by gram staining and periodic acid Schiff (PAS) staining. Moderate number of filamentous branching gram positive bacilli were found . The organism was recognized as a member of the actinomyces genus. PAS staining did not reveal any other organism. The aggressive course and progression of the disease affected the short bones of the involved foot. The patient was diagnosed as a case of Madura foot and was treated in the same hospital.

Published
2011

4. Evaluating a rapid molecular assay in a mobile laboratory for improved diagnosis of dengue in Bangladesh

Author

Hossain, Faria, Ghosh, Prakash, Chowdhury, Fazle Rabbi, Basher, Ariful, Ahsan, Hafez Mohammad Nazmul, Khan, Abed Hussain, Shumu, Samshad Jahan, Jahan, Tanzina, Roy, Chandan Kumar, Arefin, A.K.M. Nahid, Khanam, Fahmida, Rahat, Md. Abu, Chowdhury, Rajashree, Uddin, Md. Rasel, Shomik, Mohammad Sohel, Maruf, Shomik, Rashid, Md. Utba, Sagar, Soumik Kha, Mithila, Nishad Tasnim, Chowdhury, Md. Arko Ayon, Kamal, Mostafa, Sharfaraz, Ashik, Ghosh, Debashis, Chowdhury, Anup, Chowdhury, Arif Hasan, Hossain, Zazeba, Arefeen, Fahad, Islam, Md. Sohidul, Rahman, S.M. Mahbubur, Al-Amin, T.M., Rashid, Abdur, Shukla, Kuntala Kumkum, Roy, Shapla, Rana, Md. Sohel, Hossain, Md. Sarwar, Siegel, Martin, Wahed, Ahmed Abd El, and Mondal, Dinesh

Published
2025
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13. Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., Rahman, Arman, Pathologie, Cancer, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., and Rahman, Arman

Published
2024

14. Image-based multiplex immune profiling of cancer tissues:translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Author

Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., Rahman, Arman, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., and Rahman, Arman

Abstract

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer.

Published
2024

17. Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer

Author

Jahangir, Chowdhury Arif, primary, Page, David B, additional, Broeckx, Glenn, additional, Gonzalez, Claudia A, additional, Burke, Caoimbhe, additional, Murphy, Clodagh, additional, Reis‐Filho, Jorge S, additional, Ly, Amy, additional, Harms, Paul W, additional, Gupta, Rajarsi R, additional, Vieth, Michael, additional, Hida, Akira I, additional, Kahila, Mohamed, additional, Kos, Zuzana, additional, van Diest, Paul J, additional, Verbandt, Sara, additional, Thagaard, Jeppe, additional, Khiroya, Reena, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Adams, Sylvia, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Burgues, Octavio, additional, Chardas, Alexandros, additional, Cheang, Maggie Chon U, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Dudgeon, Sarah N, additional, Elghazawy, Mahmoud, additional, Fernandez‐Martín, Claudio, additional, Fineberg, Susan, additional, Fox, Stephen B, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hewitt, Stephen, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Akturk, Guray, additional, Scott, Ely, additional, Kovács, Anikó, additional, Lænkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Kharidehal, Durga, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Vincent‐Salomon, Anne, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Hytopoulos, Evangelos, additional, Mahon, Sarah, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Bartlett, John, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Specht Stovgaard, Elisabeth, additional, Salgado, Roberto, additional, Gallagher, William M, additional, and Rahman, Arman, additional

Published
2024
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19. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer

Author

Page, David B, primary, Broeckx, Glenn, additional, Jahangir, Chowdhury Arif, additional, Verbandt, Sara, additional, Gupta, Rajarsi R, additional, Thagaard, Jeppe, additional, Khiroya, Reena, additional, Kos, Zuzana, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Burgues, Octavio, additional, Cheang, Maggie Chon U, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Dudgeon, Sarah N, additional, Elghazawy, Mahmoud, additional, Ely, Scott, additional, Fernandez‐Martín, Claudio, additional, Fineberg, Susan, additional, Fox, Stephen B, additional, Gallagher, William M, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hardas, Alexandros, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hewitt, Stephen, additional, Hida, Akira I, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Hytopoulos, Evangelos, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kahila, Mohamed, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Kharidehal, Durga, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Kovács, Anikó, additional, Laenkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rahman, Arman, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Reis‐Filho, Jorge S, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Salomon, Anne‐Vincent, additional, Salto‐Tellez, Manuel, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, van Diest, Paul J, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Vieth, Michael, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Adams, Sylvia, additional, Bartlett, John Mark Seaverns, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Salgado, Roberto, additional, Specht Stovgaard, Elisabeth, additional, Akturk, Guray, additional, and Bouchmaa, Najat, additional

Published
2023
Full Text
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20. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

Author

Thagaard, Jeppe, primary, Broeckx, Glenn, additional, Page, David B, additional, Jahangir, Chowdhury Arif, additional, Verbandt, Sara, additional, Kos, Zuzana, additional, Gupta, Rajarsi, additional, Khiroya, Reena, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Akturk, Guray, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Amgad, Mohamed, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Balslev, Eva, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Bouchmaa, Najat, additional, Burgues, Octavio, additional, Chardas, Alexandros, additional, Chon U Cheang, Maggie, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dahl, Anders B, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Doré Hansen, Johan, additional, Dudgeon, Sarah N, additional, Ebstrup, Thomas, additional, Elghazawy, Mahmoud, additional, Fernandez‐Martín, Claudio, additional, Fox, Stephen B, additional, Gallagher, William M, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hauberg, Søren, additional, Hewitt, Stephen, additional, Hida, Akira I, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Hytopoulos, Evangelos, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kahila, Mohamed, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Kharidehal, Durga, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Kovács, Anikó, additional, Laenkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rahman, Arman, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Reis‐Filho, Jorge S, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Roslind, Anne, additional, Vincent‐Salomon, Anne, additional, Salto‐Tellez, Manuel, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Scott, Ely, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Fineberg, Susan, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, van Diest, Paul J, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Vieth, Michael, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Zin, Reena Md, additional, Adams, Sylvia, additional, Bartlett, John, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Salgado, Roberto, additional, and Specht Stovgaard, Elisabeth, additional

Published
2023
Full Text
View/download PDF

21. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer:A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Abstract

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer.

Published
2023

22. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Pathologie, Cancer, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Published
2023

23. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, Bouchmaa, Najat, Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, and Bouchmaa, Najat

Published
2023

24. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer:a report of the international immuno-oncology biomarker working group

Author

Thagaard, Jeppe, Broeckx, Glenn, Page, David B., Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dahl, Anders B., Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N., Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B., Gallagher, William M., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I., Horlings, Hugo M., Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel A.M., Kahila, Mohamed, Kataoka, Tatsuki R., Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Reis-Filho, Jorge S., Ribeiro, Joana M., Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, van Diest, Paul J., Verghese, Gregory E., Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Thagaard, Jeppe, Broeckx, Glenn, Page, David B., Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dahl, Anders B., Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N., Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B., Gallagher, William M., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I., Horlings, Hugo M., Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel A.M., Kahila, Mohamed, Kataoka, Tatsuki R., Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Reis-Filho, Jorge S., Ribeiro, Joana M., Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, van Diest, Paul J., Verghese, Gregory E., Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Abstract

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer.

Published
2023

26. 1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model

Author

Slater, Kayleigh, primary, Bosch, Rosa, additional, Smith, Kaelin Francis, additional, Jahangir, Chowdhury Arif, additional, Garcia-Mulero, Sandra, additional, Rahman, Arman, additional, O’Connell, Fiona, additional, Piulats, Josep M., additional, O’Neill, Valerie, additional, Horgan, Noel, additional, Coupland, Sarah E., additional, O’Sullivan, Jacintha, additional, Gallagher, William M., additional, Villanueva, Alberto, additional, and Kennedy, Breandán N., additional

Published
2023
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29. CD45-positive tumor infiltrating lymphocytes in early-stage hormone-positive, HER2-negative (ER+/HER2-) breast cancer: Correlation with proliferation and prognostic signature scores.

Author

Lucas, Mairi, primary, Kinsella, Zak, additional, Gonzalez, Claudia Aura, additional, Hurley, Camille, additional, Blümel, Anna, additional, Fay, Joanna, additional, O'Grady, Anthony, additional, Murphy, Verena, additional, Jahangir, Chowdhury Arif, additional, Burke, Caoimbhe, additional, Rahman, Arman, additional, Crown, John, additional, Kelly, Catherine Margaret, additional, Gallagher, William M., additional, and O'Connor, Darran, additional

Published
2022
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32. CD45-positive tumor infiltrating lymphocytes in early-stage hormone-positive, HER2-negative (ER+/HER2-) breast cancer: Correlation with proliferation and prognostic signature scores

Author

Mairi Lucas, Zak Kinsella, Claudia Aura Gonzalez, Camille Hurley, Anna Blümel, Joanna Fay, Anthony O'Grady, Verena Murphy, Chowdhury Arif Jahangir, Caoimbhe Burke, Arman Rahman, John Crown, Catherine Margaret Kelly, William M. Gallagher, and Darran O'Connor

Subjects
Cancer Research, Oncology
Abstract

e12555 Background: Tumour infiltrating lymphocytes (TILs), have been associated in higher responses to treatment and are thought to be a prognostic marker in a number of cancer types. The role of TILs in breast cancer varies depending on the molecular subtype of the disease. In hormone positive, HER2-negative breast cancer, the significance of TILs is less clear, partly due to the paucity of data in this area. We aim to assess overall TILs in early-stage, hormone-positive, HER2-negative (ER+/HER2-) breast cancer and its relationship with proliferation index, Ki67, and the 21-gene recurrence score. Methods: Archival patient tissue samples of early-stage, ER+/HER2- breast cancer from the Irish arm of the TAILORx clinical trial were used. Full-face sections of these tumours were stained with anti-CD45 antibody (DAKA clone M0701) via the automated Leica Bond III system. A watershed cell-detection algorithm from the open-source digital pathology software, QuPath, was fine-tuned to identify true cell objects and positive immune markers. Optimised detection parameters were used to calculate the percentage of overall CD45+ cells (CD45%) within the tumour area. Patient TIL categories were dichotomised into High v Low CD45%, with 10% chosen as the threshold. CD45% was further correlated with proliferation index, clinical data, and 21-gene recurrence score. Results: 409 samples were included in the analysis. The mean CD45% was 5.96, with samples ranging from 0.13 to 78.86. The majority of samples were in the range of 0-10% of CD45% positivity with 89% (n = 367) patients in this category. Stratification of the cohort by 21-gene-recurrence score (RS) into Low, Intermediate and High, showed a statistically significantly high CD45% in patients with a High RS compared to Low RS (p = 0.0015). When divided by recurrence score group, high CD45% trended toward a lower disease free survival (DFS) when compared to low CD45%, with statistical significance found in those in the Intermediate RS chemotherapy treatment arm (p = 0.009). Conclusions: The role of TILs in ER+/HER2- breast cancer is still undefined. While a High RS was associated with a higher percentage of CD45-positive lymphocytes, the impact on recurrence and response to treatment remains unclear. Further studies to assess the role of different tumour infiltrating lymphocyte phenotypes, and the spatial distribution of assessed markers, are needed.

Published
2022
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33. Differential expression of Bax‐Bcl‐2 and PARP‐1 confirms apoptosis of EAC cells in Swiss albino mice by Morus laevigata

Author

Israt Jerin, Sifat Rahi, Mahmudul Hasan, Chowdhury Arif Jahangir, Shihabul Islam, Kazi Md. Faisal Hoque, and Abu Reza

Subjects
Programmed cell death, 030309 nutrition & dietetics, Poly (ADP-Ribose) Polymerase-1, Biophysics, Apoptosis, Poly(ADP-ribose) Polymerase Inhibitors, Pharmacology, Mice, 03 medical and health sciences, 0404 agricultural biotechnology, In vivo, Animals, Cytotoxic T cell, Carcinoma, Ehrlich Tumor, Cytotoxicity, IC50, bcl-2-Associated X Protein, 0303 health sciences, Plant Extracts, Cell growth, Chemistry, Ascites, 04 agricultural and veterinary sciences, Cell Biology, 040401 food science, Proto-Oncogene Proteins c-bcl-2, DNA fragmentation, Morus, Food Science
Abstract

A safer natural alternative to treat neoplastic cells by inducing apoptosis is a prime requisite. Therefore, the current study was to evaluate the antiproliferative activity of Morus laevigata, a wild-type Mulberry species. Antioxidant and cytotoxic activity of aqueous extracts of M. laevigata leaf (MLL) and M. laevigata bark (MLB) were evaluated. The in vivo cell growth inhibition was assessed on Ehrlich's ascites carcinoma (EAC) bearing mice model. Fluorescent microscopy and expression of PARP-1, Bax, and Bcl-2 through qPCR were performed to evaluate apoptosis. MLL and MLB extracts show promising antioxidant property with an IC50 value of 186.76 µg/ml and 352.97 µg/ml, respectively, with a decent LD50 value of 99.16 µg/ml and 92.54 µg/ml for MLL and MLB extract, respectively, indicated notable cytotoxicity. Cell growth inhibition was observed using MLL and MLB extracts were 68.33% and 48.66%, respectively. The morphological alteration, DNA fragmentation, and differential expression of Bax, Bcl-2, and PARP-1 confirm the induction of the intrinsic pathway of apoptosis. PRACTICAL APPLICATIONS: Plant-based medicine always plays a tremendous role in preventing several fatal diseases like cancer. The study evaluated the anticancer activity of a wild-type mulberry. Moreover, the potent antioxidant activity of the plant makes it possible to be a great candidate for cancer remedy. Besides, the molecular expression of the genes related to apoptosis confirms the plant's bioactive compounds could be a drug lead to neoplastic cells in the future. Presences of an immense antioxidant properties urge that they can be contribute in cancer treatment through the cell death pathways.

Published
2020
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34. Advances in tissue-based imaging: impact on oncology research and clinical practice

Author

Niamh Russell, Nebras Al-Attar, Claudia Aura, Chowdhury Arif Jahangir, Seodhna M. Lynch, Arman Rahman, William M. Gallagher, and Fiona Lanigan

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Fluorescent Antibody Technique, Medical Oncology, Pathology and Forensic Medicine, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, Neoplasms, Genetics, Biomarkers, Tumor, Image Processing, Computer-Assisted, Tumor Microenvironment, Medicine, Medical physics, Practice Patterns, Physicians', Molecular Biology, business.industry, Disease Management, Traction (orthopedics), Immunohistochemistry, Molecular Imaging, Clinical Practice, 030104 developmental biology, 030220 oncology & carcinogenesis, Molecular Medicine, business
Abstract

Tissue-based imaging has emerged as a critical tool in translational cancer research and is rapidly gaining traction within a clinical context. Significant progress has been made in the digital pathology arena, particularly in respect of brightfield and fluorescent imaging. Critically, the cellular context of molecular alterations occurring at DNA, RNA, or protein level within tumor tissue is now being more fully appreciated. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumor microenvironment, including the potential interplay between various cell types.This review summarizes the recent developments within the field of tissue-based imaging, centering on the application of these approaches in oncology research and clinical practice.Significant advances have been made in digital pathology during the last 10 years. These include the use of quantitative image analysis algorithms, predictive artificial intelligence (AI) on large datasets of HE images, and quantification of fluorescence multiplexed tissue imaging data. We believe that new methodologies that can integrate AI-derived histologic data with omic data, together with other forms of imaging data (such as radiologic image data), will enhance our ability to deliver better diagnostics and treatment decisions to the cancer patient.

Published
2020

38. Development of predictive models for skid resistance of asphalt pavements and seal coat.

Author

Aldagari, Sand, Al-Assi, Mohammad, Kassem, Emad, Chowdhury, Arif, and Masad, Eyad

Subjects
SKID resistance, ASPHALT pavements, MECHANICAL abrasion, PREDICTION models, ASPHALT testing, SLIDING friction, PAVEMENT testing
Abstract

Skid resistance is a key factor in road safety. Surface friction characteristics of roads are dependent on the microtexture and macrotexture of the surface. The decay of skid resistance with time is a function of traffic level and aggregate characteristics. This study developed predictive models for skid resistance of asphalt pavements and seal coat surfaces. The researchers examined the surface friction characteristics of 35 asphalt pavement test sections and 35 seal coat test sections. The skid number was measured using a skid trailer, while the microtexture and macrotexture of the test sections were measured using a dynamic friction tester and a circular texture meter, respectively. The Aggregate Image Measurement System (AIMS) and Micro-Deval test were also used to evaluate the aggregate shape properties and its resistance to polishing and abrasion. The developed skid prediction models express the skid number over time as a function of aggregate gradation, aggregate resistance to abrasion and polishing, and traffic level. The models showed good correlations with skid numbers measured in the field. These models can be used to optimise the mix design to provide adequate level of friction and estimate the skid number of asphalt pavements and seal coat surfaces over time. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Deciphering the molecular pathways of apoptosis using leaf extract of Basella alba against Ehrlichs Ascites Carcinoma (EAC) cell line in Swiss albino mice model

Author

Salek Ahmed Sajib, Ariful Haque, Chowdhury Arif Jahangir, Md. Mahmudul Hasan, Md. Shihabul Islam, Md. Sifat Rahi, Syed Rashel Kabir, Kazi Md. Faisal Hoque, Mohammad Ali Moni, and Md. Abu Reza

Subjects
chemistry.chemical_compound, Programmed cell death, law, Chemistry, Cell culture, Apoptosis, Cell growth, DNA fragmentation, Gene, Polymerase chain reaction, DNA, law.invention, Cell biology
Abstract

A series of programmed cell death that plays a vital role in the exclusion of abnormal cells without any ruin into the surrounding neighboring cells is called Apoptosis. Generally, it occurs in multi-cellular organisms through an orderly and autonomously processes that is controlled by proper function of various genes. In the current studies, cell apoptosis in EAC cells treated with different fractions (BLP-01, BLP-02 and BLP-03) of leaf ex- tract of B. alba was detected by conducting several bio-assays such as cell growth inhibition, fluorescence and optical microscopy, DNA fragmentation and PCR amplification etc. The results of these experiments indicate that the plant extracts are able to inhibit cell growth significantly where morphological features of apoptosis were appeared under both fluorescence and optical microscope. The PCR amplification results showed that the leaf ex- tracts of B. alba were able to cause EAC cell apoptosis in both the extrinsic and intrinsic pathway. An excellent figure of fragmented DNA was found in DNA fragmentation assay when the gel was observed under UV light which confirms the cell apoptosis. The current findings suggest that the samples of this experiment occupy fascinating competence to conduct cell apoptosis and become an ideal resource for cancer research as well as drugs development for cancer treatment.

Published
2018
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41. In Vivo Anticancer Activity of Basella alba Leaf and Seed Extracts against Ehrlich's Ascites Carcinoma (EAC) Cell Line

Author

Habibur Rahman, Ruhul Amin, Kazi Md. Faisal Hoque, Israt Jerin, Md. Sifat Rahi, Chowdhury Arif Jahangir, Abu Reza, and Md. Shihabul Islam

Subjects
0301 basic medicine, Article Subject, Cell growth, Cancer, food and beverages, lcsh:Other systems of medicine, DNA laddering, Pharmacology, medicine.disease, lcsh:RZ201-999, Ehrlich ascites carcinoma, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Complementary and alternative medicine, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Cancer cell, medicine, Growth inhibition, Fragmentation (cell biology), Research Article
Abstract

Cancer is a class of diseases characterized by uncontrolled cell growth. The current treatment options of cancer are radiotherapy, chemotherapy, hormone therapy, and surgery, where all of them have unpleasant side effects. Due to their adverse side effects, it is challenging to develop new drug for cancer treatment. Hence, the scientists are trying to seek for noble compounds from natural sources to treat cancer. Therefore, in the present investigation, a widely consumable vegetableBasella albawas subjected to evaluate its antiproliferative effect along with molecular signaling of apoptosis in Ehrlich ascites carcinoma (EAC) cell line. Cell growth inhibition was determined by haemocytometer whereas apoptosis of cancer cells were studied by florescence microscope using Hoechst-33342 stain and result was supported by DNA fragmentation and certain cancer related genes expression through PCR analysis.B. albaleaf and seed extract exhibit a considerable scavenging activity in comparison to a standard antioxidant BHT. Moreover, the leaf and seed extracts were able to agglutinate 2% RBC of goat blood at minimum 12.5μg/ml and 50.0μg/ml concentration, respectively. A significant cytotoxic activity was also found in both leaf and seed extract. In haemocytometic observation, the leaf and seed extracts exhibit about 62.54±2.41% and 53.96±2.34% cell growth inhibition, respectively, whereas standard anticancer drug Bleomycin showed 79.43±1.92% growth inhibition. Morphological alteration under fluorescence microscope showed nuclear condensation and fragmentation which is the sign of apoptosis. Apoptosis induction was also confirmed by DNA laddering in leaf and seed treated EAC cells. Upregulation of the tumor suppressor gene P53and downregulation of antiapoptotic gene Bcl-2 enumerate apoptosis induction. Therefore, current study manifested that leaf and seed extracts ofB. albahave antiproliferative activity against EAC cell line and can be a potent source of anticancer agents to treat cancer.

Published
2018

45. Surface-Charge-Controlled Synthesis of ZnIn2S4 Nanosheet-Based Materials for Selective Adsorption of Organic Dyes.

Author

Khan, Afaq Ahmad, Molla, Aniruddha, Chowdhury, Arif, Kumari, Sunita, and Hussain, Sahid

Abstract

In recent years, controlling and manipulating the materials' surface charges have gained significant attention because of efficient application in various fields such as catalysis, dye adsorption, chromatography, etc. In this study, we have controlled the surface charge of ZnIn2S4 nanomaterials (NMs) by loading Zn2+ ions on the surface of materials. The ζ-potential studies revealed that the average surface charge of the NMs was successfully controlled from −30.3 to +31.4 mV. The X-ray diffraction patterns suggested that the phase of the NMs is changed from hexagonal ZnIn2S4 to cubic ZnIn2S4 with slight trigonal ZnS moieties. Further, the electron microscopy results displayed that the morphology of the NMs gradually changed from a sheetlike structure to a hybrid of sphere/petals and finally a very small flakelike structure with an increasing loading concentration of Zn2+ ions. Moreover, the nanosheet micrograph showed the different numbers of sheet layers, which are composed of 2–6 layers. The Brunauer–Emmett–Teller analysis indicated that the specific surface area is increased from 48.2 to 118.6 m2 g–1 after the loading of Zn2+ ions. The obtained NMs displayed a high adsorption selectivity performance for organic dyes. A separation factor (α21) of 95% was obtained for anionic Congo red (CR) over positively charged nanoflakes and 85% for cationic methylene blue (MB) dyes on negatively charged nanosheet. The as-prepared nanosheet and nanoflakes also showed efficient adsorption behavior toward two different kinds of antibiotics such as tetracycline and ciprofloxacin. The adsorption process followed the Langmuir isotherm model for the MB, CR, and ciprofloxacin, whereas tetracycline adsorption obeyed the Freundlich isotherm model. The adsorbents displayed a pseudo-second-order rate kinetic model. The recyclability of the best adsorbents was found up to five times without significant loss of removal efficiency. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Deciphering the molecular pathways of apoptosis using leaf extract of Basella alba against Ehrlichs Ascites Carcinoma (EAC) cell line in Swiss albino mice model

Author

Islam, Md. Shihabul, primary, Rahi, Md. Sifat, additional, Jahangir, Chowdhury Arif, additional, Hasan, Md. Mahmudul, additional, Sajib, Salek Ahmed, additional, Haque, Ariful, additional, Kabir, Syed Rashel, additional, Hoque, Kazi Md. Faisal, additional, Moni, Mohammad Ali, additional, and Reza, Md. Abu, additional

Published
2018
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