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Indraneel Mittra

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Indraneel Mittra
Born (1943-06-28) 28 June 1943 (age 81)
New Delhi, India
NationalityIndian
Alma materDelhi University, Royal College of Surgeons of England, London University
Known forPioneering breast cancer surgery as an specialty discipline in India.

Conducting the Mumbai Study of early detection of breast and cervical cancer.

Discovering the pathological effects of cell-free chromatin particles and their mitigation with therapeutic effects in human diseases.[1][2][3]
Scientific career
FieldsCancer surgery

Laboratory science

Public health research
Academic advisorsIsrael Doniach; Renato Dulbecco

Indraneel Mittra FRCS (England),[4] FASc,[4] FNA[5] (born 28 June 1943) is an Indian cancer surgeon, basic research scientist, and public health researcher. He is the Dr. Ernest Borges Chair in Translational Research and Professor Emeritus in the Department of Surgical Oncology, Tata Memorial Centre (TMC) in Mumbai.[4] He established the first dedicated multi-disciplinary Breast Unit in India[4] – a model which has since been adopted by most centers in the country. He pioneered the discipline of clinical research in cancer in India and pursued the cause of improving cancer care in the developing world.[6][7][8][9][10][11][12][13] In this context, and with an RO1 grant from the National Institutes of Health (NIH) of the United States, Mittra spearheaded one of the largest randomized trials of screening for early detection of breast and cervical cancer using low-cost technology approaches involving 150,000 women in the suburbs of Mumbai.[14][15][16] He is the first Indian recipient of such a competitive grant from the NIH.[17] In the field of laboratory research, he is credited with having discovered the wide-ranging biological activities of cell-free chromatin particles (cfChPs), which have critical implications for human health and disease, and how deactivating cfChPs can have many therapeutic effects.[1][18][19][20][21][22][23][24] Prof. Mittra’s current research interests revolve around studying cfChPs in the context of evolution.

Biography

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Mittra was born in New Delhi in 1943 to a family of doctors, with both his father and grandfather being eminent physicians. Mittra studied medicine at the Maulana Azad Medical College, University of Delhi and graduated in 1965.[25] He received his surgical training in the UK at the Hammersmith Hospital and Royal Postgraduate Medical School (now amalgamated with Imperial College, London), Royal Sussex County Hospital, and Guy’s Hospital in London.[25] He subsequently became a Fellow of the Royal College of Surgeons of England in 1971,[4] and received his PhD in Medicine (cancer biology) from the University of London in 1977[4] under the guidance of Professor Israel Doniach. He then completed his post-doctoral training under Nobel Laureate Dr. Renato Dulbecco at the Imperial Cancer Research Fund Laboratories in London[4] (now amalgamated with Cancer Research UK). He followed this up with a stint at St Bartholomew's Hospital and the Institute of Cancer Research in London as a Post-doctoral Fellow.[4]

Legacy

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On returning to India in 1982, Mittra joined the Tata Memorial Centre as a consultant surgical oncologist.[4] His most significant legacy is to have inspired an entire generation of young clinicians towards the path of critical thinking, intellectual inquiry, and scientific temper which played a role in transforming TMC from a service hospital to a vibrant academic institution that is now affiliated to the Homi Bhabha National Institute – a deemed university.[26][27] Mittra is considered to be the founder of breast cancer surgery as a specialty discipline in India. He became Professor Surgical Oncology and Chief of Surgical Breast Service[25] at TMC and trained and mentored many surgeons who are now renowned in their own right. In the field of public health research, his randomized trial of screening for early detection of breast cancer using clinical breast examination, and of cervical cancer using visual inspection of the cervix, involving 150,000 women, is considered to be a landmark study that can save thousands of lives annually if implemented in low- and middle-income countries.[28][29][30][31] With regard to laboratory research, Mittra made his first scientific contribution as a single author paper in the journal Nature in 1974.[32] This publication opened up many research avenues on the role of the thyroid hormone in breast cancer and its relationship with prolactin.[33][34][35][36][37][38][39] He has worked extensively on prognostic factors in breast cancer and their relationship with treatment outcomes.[40][39][41][42][43] In the last 20 years, Mittra’s research has revolved around the consequences of cell death and the myriad biological activities surrounding cell-free chromatin particles (cfChPs) that emerge from dying cells.[18][44] His research has led to the discovery of the role of cfChPs in chemotherapy-[19][45] and radiotherapy-[20] induced toxicity, sepsis,[21][46][47] ageing,[22][48] cancer,[23][49] and the immune system.[24] Mittra has also discovered how the harmful effects of cfChPs can be mitigated by combining the nutraceuticals Resveratrol (R) and Copper (Cu).[50] He has shown that the R-Cu combination leads to the generation of oxygen radicals, which can deactivate cfChPs with therapeutic effects.[19][20][21][22][23][45][46][47][48][49] Mittra has successfully shown that R-Cu treatment is effective in humans in reducing toxicity from chemotherapy,[2][3] prevention of death from severe COVID-19,[1] and reversing the aggressive behavior of cancer.[23]

Awards and recognition

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Mittra was elected to the fellowship of the Indian Academy of Sciences[4] and Indian National Science Academy[4] in recognition of his contribution to the field of cancer. He held the Pearce Goulde professorship at University College London (1999).[4]  Mittra has been on the editorial/advisory boards of The British Medical Journal, The Lancet Oncology, Nature Reviews Clinical Oncology, the British Journal of Cancer, European Journal of Cancer, among others.[4] He holds a US patent (no. US 9,096,655 B2) titled “Method for in-vivo binding of chromatin fragments”.[51]

References

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  1. ^ a b c Mittra, Indraneel; de Souza, Rosemarie; Bhadade, Rakesh; Madke, Tushar; Shankpal, P.D.; Joshi, Mohan; Qayyumi, Burhanuddin; Bhattacharjee, Atanu; Gota, Vikram; Gupta, Sudeep; Chaturvedi, Pankaj; Badwe, Rajendra (2020). "Resveratrol and Copper for treatment of severe COVID-19: an observational study (RESCU 002)". doi:10.1101/2020.07.21.20151423. S2CID 220834653. {{cite journal}}: Cite journal requires |journal= (help)
  2. ^ a b Agarwal, Anshul; Khandelwal, Aakanksha; Pal, Kavita; Khare, Naveen Kumar; Jadhav, Vishal; Gurjar, Murarilal; Punatar, Sachin; Gokarn, Anant; Bonda, Avinash; Nayak, Lingaraj; Kannan, Sadhana; Gota, Vikram; Khattry, Navin; Mittra, Indraneel (2022-02-04). "A novel pro-oxidant combination of resveratrol and copper reduces transplant related toxicities in patients receiving high dose melphalan for multiple myeloma (RESCU 001)". PLOS ONE. 17 (2): e0262212. Bibcode:2022PLoSO..1762212A. doi:10.1371/journal.pone.0262212. ISSN 1932-6203. PMC 8815866. PMID 35120140.
  3. ^ a b Ostwal, Vikas; Ramaswamy, Anant; Bhargava, Prabhat; Srinivas, Sujay; Mandavkar, Sarika; Chaugule, Deepali; Peelay, Zoya; Baheti, Akshay; Tandel, Harshali; Jadhav, Vishal Kumar; Shinde, Sushma; Jadhav, Shraddha; Gota, Vikram; Mittra, Indraneel (2022-11-13). "A pro-oxidant combination of resveratrol and copper reduces chemotherapy-related non-haematological toxicities in advanced gastric cancer: results of a prospective open label phase II single-arm study (RESCU III study)". Medical Oncology. 40 (1): 17. doi:10.1007/s12032-022-01862-1. ISSN 1559-131X. PMID 36372825. S2CID 253501056.
  4. ^ a b c d e f g h i j k l m "Indian Fellows – Indian National Science Academy". Retrieved 2023-08-09.
  5. ^ "Fellowship | Indian Academy of Sciences". opsias.ias.ac.in. Retrieved 2023-08-09.
  6. ^ Mittra, I (January 1997). "Clinical cancer trials in developing countries". The Lancet. 349 (9047): 290. doi:10.1016/s0140-6736(05)64908-2. ISSN 0140-6736. PMID 9014946. S2CID 28184865.
  7. ^ Mittra, I.; Badwe, R.A.; Desai, P.B.; Yeole, B.B.; Jussawalla, D.J. (April 1989). "Early Detection of Breast Cancer in Developing Countries". The Lancet. 333 (8640): 719–720. doi:10.1016/s0140-6736(89)92229-0. ISSN 0140-6736. PMID 2564524. S2CID 46091017.
  8. ^ Tobias, J.S.; Mittra, I. (April 1993). "Improving cancer care world wide". Annals of Oncology. 4 (4): 283–287. doi:10.1093/oxfordjournals.annonc.a058483. ISSN 0923-7534. PMID 8518217.
  9. ^ Pai, Sanjay A (December 2000). "Challenging cancer in developing countries". The Lancet Oncology. 1 (4): 203. doi:10.1016/s1470-2045(05)70068-1. ISSN 1470-2045. PMID 11905632.
  10. ^ Mittra, Indraneel (2011-09-01). "Breast cancer screening in developing countries". Preventive Medicine. Special Section: Breast Cancer Screening. 53 (3): 121–122. doi:10.1016/j.ypmed.2011.06.010. ISSN 0091-7435. PMID 21712052.
  11. ^ Boulos, S; Gadallah, M; Neguib, S; Essam, Ea; Youssef, A; Costa, A; Mittra, I; Miller, AB (October 2005). "Breast screening in the emerging world: High prevalence of breast cancer in Cairo". The Breast. 14 (5): 340–346. doi:10.1016/j.breast.2005.07.002. ISSN 0960-9776. PMID 16131468.
  12. ^ Mittra, I. (February 1994). "Breast screening: the case for physical examination without mammography". The Lancet. 343 (8893): 342–344. doi:10.1016/s0140-6736(94)91170-3. ISSN 0140-6736. PMID 7905152. S2CID 41172953.
  13. ^ Mittra, Indraneel; Baum, Michael; Thornton, Hazel; Houghton, Joan (2000-10-28). "Is clinical breast examination an acceptable alternative to mammographic screening?". BMJ. 321 (7268): 1071–1073. doi:10.1136/bmj.321.7268.1071. ISSN 0959-8138. PMC 1118853. PMID 11053185.
  14. ^ "Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai". BMJ. 372: n738. 2021-03-19. doi:10.1136/bmj.n738. ISSN 1756-1833. PMC 7977439. PMID 33741550.
  15. ^ Shastri, S. S.; Mittra, I.; Mishra, G. A.; Gupta, S.; Dikshit, R.; Singh, S.; Badwe, R. A. (2014-02-22). "Effect of VIA Screening by Primary Health Workers: Randomized Controlled Study in Mumbai, India". JNCI Journal of the National Cancer Institute. 106 (3): dju009. doi:10.1093/jnci/dju009. ISSN 0027-8874. PMC 3982783. PMID 24563518.
  16. ^ Mittra, Indraneel; Mishra, Gauravi A.; Singh, Shalini; Aranke, Sangeeta; Notani, Perin; Badwe, Rajendra; Miller, Anthony B.; Daniel, Elkan E.; Gupta, Subhadra; Uplap, Pallavi; Thakur, Meenakshi H.; Ramani, Subhash; Kerkar, Rajendra; Ganesh, Balasubramanian; Shastri, Surendra S. (2009). "A cluster randomized, controlled trial of breast and cervix cancer screening in Mumbai, India: Methodology and interim results after three rounds of screening". International Journal of Cancer. 126 (4): 976–984. doi:10.1002/ijc.24840. PMID 19697326.
  17. ^ "Surgery". Doctor.ndtv.com. Retrieved 2023-08-09.
  18. ^ a b Mittra, Indraneel; Samant, Urmila; Sharma, Suvarna; Raghuram, Gorantla V.; Saha, Tannistha; Tidke, Pritishkumar; Pancholi, Namrata; Gupta, Deepika; Prasannan, Preeti; Gaikwad, Ashwini; Gardi, Nilesh; Chaubal, Rohan; Upadhyay, Pawan; Pal, Kavita; Rane, Bhagyeshri (2017-05-29). "Cell-free chromatin from dying cancer cells integrate into genomes of bystander healthy cells to induce DNA damage and inflammation". Cell Death Discovery. 3 (1): 17015. doi:10.1038/cddiscovery.2017.15. ISSN 2058-7716. PMC 5447133. PMID 28580170.
  19. ^ a b c Mittra, I.; Pal, K.; Pancholi, N.; Shaikh, A.; Rane, B.; Tidke, P.; Kirolikar, S.; Khare, N.K.; Agrawal, K.; Nagare, H.; Nair, N.K. (September 2017). "Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin". Annals of Oncology. 28 (9): 2119–2127. doi:10.1093/annonc/mdx318. ISSN 0923-7534. PMID 28911066.
  20. ^ a b c Kirolikar, Saurabh; Prasannan, Preeti; Raghuram, Gorantla V.; Pancholi, Namrata; Saha, Tannishtha; Tidke, Pritishkumar; Chaudhari, Pradip; Shaikh, Alfina; Rane, Bhagyeshri; Pandey, Richa; Wani, Harshada; Khare, Naveen K.; Siddiqui, Sophiya; D’souza, Jenevieve; Prasad, Ratnam (2018-11-15). "Prevention of radiation-induced bystander effects by agents that inactivate cell-free chromatin released from irradiated dying cells". Cell Death & Disease. 9 (12): 1142. doi:10.1038/s41419-018-1181-x. ISSN 2041-4889. PMC 6238009. PMID 30442925.
  21. ^ a b c Mittra, Indraneel; Pal, Kavita; Pancholi, Namrata; Tidke, Pritishkumar; Siddiqui, Sophiya; Rane, Bhagyeshri; D’souza, Jenevieve; Shaikh, Alfina; Parab, Saili; Shinde, Sushma; Jadhav, Vishal; Shende, Soniya; Raghuram, Gorantla V. (2020-03-04). "Cell-free chromatin particles released from dying host cells are global instigators of endotoxin sepsis in mice". PLOS ONE. 15 (3): e0229017. Bibcode:2020PLoSO..1529017M. doi:10.1371/journal.pone.0229017. ISSN 1932-6203. PMC 7055819. PMID 32130239.
  22. ^ a b c Pal, Kavita; Raghuram, Gorantla V.; Dsouza, Jenevieve; Shinde, Sushma; Jadhav, Vishalkumar; Shaikh, Alfina; Rane, Bhagyeshri; Tandel, Harshali; Kondhalkar, Dipali; Chaudhary, Shahid; Mittra, Indraneel (2022-10-14). "A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration in mice". Scientific Reports. 12 (1): 17209. Bibcode:2022NatSR..1217209P. doi:10.1038/s41598-022-21388-w. ISSN 2045-2322. PMC 9568542. PMID 36241685.
  23. ^ a b c d Pilankar, Aishwarya; Singhavi, Hitesh; Raghuram, Gorantla V.; Siddiqui, Sophiya; Khare, Naveen Kumar; Jadhav, Vishalkumar; Tandel, Harshali; Pal, Kavita; Bhattacharjee, Atanu; Chaturvedi, Pankaj; Mittra, Indraneel (2022). "A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: Results of an exploratory study (RESCU 004)". Frontiers in Oncology. 12. doi:10.3389/fonc.2022.1000957. ISSN 2234-943X. PMC 9525028. PMID 36185249.
  24. ^ a b Shabrish, Snehal; Pal, Kavita; Khare, Naveen Kumar; Satsangi, Dharana; Pilankar, Aishwarya; Jadhav, Vishalkumar; Shinde, Sushma; Raphael, Nimisha; Sriram, Gaurav; Lopes, Relestina; Raghuram, Gorantla V.; Tandel, Harshali; Mittra, Indraneel (June 2023). "Cell-free chromatin particles activate immune checkpoints in human T cells: Implications for cancer therapy". bioRxiv. doi:10.1101/2023.06.09.544311. S2CID 259156310.
  25. ^ a b c "ORCID". orcid.org. Retrieved 2023-08-11.
  26. ^ "Thread by @cspramesh on Thread Reader App". threadreaderapp.com. Retrieved 2023-08-17.
  27. ^ "Homi Bhabha National Institute", Wikipedia, 2023-08-11, retrieved 2023-08-17
  28. ^ Mittra, Indraneel (2021-02-24). "The story of the Mumbai breast screening study". The BMJ. Retrieved 2023-08-17.
  29. ^ Wangchuk, Rinchen Norbu (2021-03-31). "Indian Surgeon's Groundbreaking Cancer Research Has Saved 1000s of Lives". The Better India. Retrieved 2023-08-17.
  30. ^ Abraham, Jame; MD; FACP (April 10, 2021). "Breast Cancer Screening With Clinical Breast Examination in Low- and Middle-Income Countries - The ASCO Post". ascopost.com. Retrieved 2023-08-17.
  31. ^ "World's largest trial on breast cancer screening: The backstory". The Times of India. ISSN 0971-8257. Retrieved 2023-08-17.
  32. ^ Mittra, I. (April 1974). "Mammotropic effect of prolactin enhanced by thyroidectomy". Nature. 248 (5448): 525–526. Bibcode:1974Natur.248..525M. doi:10.1038/248525a0. ISSN 1476-4687. PMID 4824351. S2CID 4265881.
  33. ^ Mittra, I.; Hayward, J.L. (May 1974). "Hypothalamic-Pituitary-Thyroid Axis in Breast Cancer". The Lancet. 303 (7863): 885–889. doi:10.1016/s0140-6736(74)90344-4. ISSN 0140-6736. PMID 4133416.
  34. ^ Mittra, I.; Hayward, J.L.; Mcneilly, A.S. (May 1974). "Hypothalamic-Pituitary-Prolactin Axis in Breast Cancer". The Lancet. 303 (7863): 889–891. doi:10.1016/s0140-6736(74)90345-6. ISSN 0140-6736. PMID 4133417.
  35. ^ Mittra, I.; Perrin, J.; Kumaoka, S. (1976-01-31). "Thyroid and other autoantibodies in British and Japanese women: an epidemiological study of breast cancer". Br Med J. 1 (6004): 257–259. doi:10.1136/bmj.1.6004.257. ISSN 0007-1447. PMC 1638530. PMID 1082357.
  36. ^ Mittra, Indraneel (1980-08-29). "A novel "Cleaved Prolactin" in the rat pituitary: Part I biosynthesis, characterization and regulatory control". Biochemical and Biophysical Research Communications. 95 (4): 1750–1759. doi:10.1016/S0006-291X(80)80101-X. ISSN 0006-291X. PMID 7417342.
  37. ^ Mittra, Indraneel (1980-08-29). "A novel "Cleaved Prolactin" in the rat pituitary: Part II in vivo mammary mitogenic activity of its N-terminal 16K moiety". Biochemical and Biophysical Research Communications. 95 (4): 1760–1767. doi:10.1016/S0006-291X(80)80102-1. ISSN 0006-291X. PMID 7417343.
  38. ^ Mittra, Indraneel (September 1984). "Somatomedins and proteolytic bioactivation of prolactin and growth hormone". Cell. 38 (2): 347–348. doi:10.1016/0092-8674(84)90488-4. ISSN 0092-8674. PMID 6380763. S2CID 31474305.
  39. ^ a b Mittra, I. (1975-10-01). "Potency of thyroid hormone analogues in suppressing prolactin-mediated mammary growth in thyroidectomized rats". Experientia. 31 (10): 1218–1221. doi:10.1007/BF02326803. ISSN 0014-4754. PMID 1204749. S2CID 32270204.
  40. ^ Vaidya, J. S.; Vyas, J. J.; Chinoy, R. F.; Merchant, N.; Sharma, O. P.; Mittra, I. (1996). "Multicentricity of breast cancer: whole-organ analysis and clinical implications". British Journal of Cancer. 74 (5): 820–824. doi:10.1038/bjc.1996.442. ISSN 1532-1827. PMC 2074702. PMID 8795588.
  41. ^ Mittra, Indraneel; Redkar, Alka A.; Badwe, Rajan A. (October 1995). "Prognosis of breast cancer: Evidence for interaction between c-erbB-2 overexpression and number of involved axillary lymph nodes". Journal of Surgical Oncology. 60 (2): 106–111. doi:10.1002/jso.2930600208. PMID 7564375. S2CID 26538092.
  42. ^ Mittra, Indraneel; MacRae, Kenneth D. (1991-12-01). "A meta-analysis of reported correlations between prognostic factors in breast cancer: Does axillary lymph node metastasis represent biology or chronology?". European Journal of Cancer and Clinical Oncology. 27 (12): 1574–1583. doi:10.1016/0277-5379(91)90418-D. ISSN 0277-5379. PMID 1838260.
  43. ^ Mittra, Indraneel (January 1993). "Axillary lymph node metastasis in breast cancer: Prognostic indicator or lead-time bias?". European Journal of Cancer. 29 (3): 300–302. doi:10.1016/0959-8049(93)90371-l. ISSN 0959-8049. PMID 8398321.
  44. ^ Mittra, Indraneel; Khare, Naveen Kumar; Raghuram, Gorantla Venkata; Chaubal, Rohan; Khambatti, Fatema; Gupta, Deepika; Gaikwad, Ashwini; Prasannan, Preeti; Singh, Akshita; Iyer, Aishwarya; Singh, Ankita; Upadhyay, Pawan; Nair, Naveen Kumar; Mishra, Pradyumna Kumar; Dutt, Amit (2015-03-01). "Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes". Journal of Biosciences. 40 (1): 91–111. doi:10.1007/s12038-015-9508-6. ISSN 0973-7138. PMC 5779614. PMID 25740145.
  45. ^ a b Helleday, T. (2017). "Chemotherapy-induced toxicity—a secondary effect caused by released DNA?". Annals of Oncology. 28 (9): 2054–2055. doi:10.1093/annonc/mdx349. ISSN 0923-7534. PMID 28911088.
  46. ^ a b lorianpayne (2021-02-25). "How cell-free chromatin particles could be the missing link to the long-awaited treatment of sepsis". Research Features. Retrieved 2023-08-17.
  47. ^ a b "Scientists uncover key molecular mechanism underlying different aspects of sepsis". News-Medical.net. 2020-03-27. Retrieved 2023-08-17.
  48. ^ a b Cancer (ACTREC), Advanced Centre for Treatment, Research & Education in. "Indian Researchers from ACTREC Discover Novel Therapeutic Agent for a Host of Diseases". www.prnewswire.com (Press release). Retrieved 2023-08-17.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  49. ^ a b "Exploiting the synergy of nutraceuticals for cancer prevention and treatment". EurekAlert!. Retrieved 2023-08-17.
  50. ^ Subramaniam, Siddharth; Vohra, Iqbal; Iyer, Aishwarya; Nair, Naveen K.; Mittra, Indraneel (2016-03-02). "A paradoxical relationship between Resveratrol and copper (II) with respect to degradation of DNA and RNA". F1000Research. 4 (4:1145): 1145. doi:10.12688/f1000research.7202.2. PMC 4833056. PMID 27134724.
  51. ^ US 9096655, Mittra, Indraneel; Ramesan, Rekha Mannemcherril & Sharma, Chandra Prakash et al., "Method for in-vivo binding of chromatin fragments", published 2015-08-04, assigned to Tata Memorial Centre 
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