Publications by authors named "Pranshu Bansal"

14 Publications

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The MK2 pathway is linked to G-CSF, cytokine production and metastasis in gastric cancer: a novel intercorrelation analysis approach.

J Transl Med 2020 03 26;18(1):137. Epub 2020 Mar 26.

Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

Background: Gastric cancer is associated with chronic inflammation, but there is still much to understand about the tumor microenvironment and the underlying tumor-promoting mechanisms. The Map kinase-activated protein kinase 2 (MK2) pathway is a regulator of inflammatory cytokine production that we have been studying in gastrointestinal cancers. Here, we set out to determine the significance of this gene in gastric cancer along with its downstream mediators and if there were differences in the primary tumors with and without metastasis.

Methods: Human gastric cancer tissues with and without metastasis were examined for MK2 expression and cytokine profile in organ culture supernatants. Advanced statistical methods including a lower triangular correlation matrix, novel rooted correlation network, linear and logistic regression modeling along with Kruskal-Wallis testing with Sidak correction for multiple testing were applied to gain understanding of cytokines/chemokines linked to metastasis.

Results: The MK2 pathway is strongly linked with metastasis and a panel of cytokines. Gene expression was able to classify gastric cancer metastasis 85.7% of the time. A significant association with a panel of cytokines was found, including G-CSF, GM-CSF, Mip-1β, IFN-α, MCP-1, IL-1β, IL-6, and TNF-α. Mip-1β was found to have the strongest association with MK2 and metastasis after Sidak correction for multiple testing.

Conclusions: MK2 gene expression and a novel associated cytokine panel are linked to gastric cancer metastasis. G-CSF is the strongest cytokine to differentiate between metastasis and non-metastasis patients and had the lowest P value, while Mip-1β showed the strongest association with MK2 and metastasis after Sidak correction. MK2 and associated cytokines are potential biomarkers for gastric cancer metastasis. The novel intercorrelation analysis approach is a promising method for understanding the complex nature of cytokine/chemokine regulation and links to disease outcome.
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http://dx.doi.org/10.1186/s12967-020-02294-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098132PMC
March 2020

Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.

Adv Ther 2019 10 13;36(10):2638-2678. Epub 2019 Aug 13.

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

In the last few years, immunotherapy has transformed the way we treat solid tumors, including melanoma, lung, head neck, breast, renal, and bladder cancers. Durable responses and long-term survival benefit has been experienced by many cancer patients, with favorable toxicity profiles of immunotherapeutic agents relative to chemotherapy. Cures have become possible in some patients with metastatic disease. Additional approvals of immunotherapy drugs and in combination with other agents are anticipated in the near future. Multiple additional immunotherapy drugs are in earlier stages of clinical development, and their testing in additional tumor types is under way. Despite considerable early success and relatively fewer side effects, the majority of cancer patients do not respond to checkpoint inhibitors. Additionally, while the drugs are generally well tolerated, there is still the potential for significant, unpredictable and even fatal toxicity with these agents. Improved biomarkers may help to better select patients who are more likely to respond to these drugs. Two key biologically important predictive tissue biomarkers, specifically, PD-L1 and mismatch repair deficiency, have been FDA-approved in conjunction with the checkpoint inhibitor, pembrolizumab. Tumor mutation burden, another promising biomarker, is emerging in several tumor types, and may also soon receive approval. Finally, several other tissue and liquid biomarkers are emerging that could help guide single-agent immunotherapy and in combination with other agents. Of these, one promising investigational biomarker is alteration or deficiency in DNA damage response (DDR) pathways, with altered DDR observed in a broad spectrum of tumors. Here, we provide a critical overview of current, emerging, and investigational biomarkers in the context of response to immunotherapy in solid tumors.
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http://dx.doi.org/10.1007/s12325-019-01051-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778545PMC
October 2019

Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer.

Oncologist 2018 01 20;23(1):2-e5. Epub 2017 Nov 20.

Santa Clara Valley Medical Center, San Jose, California, USA.

Lessons Learned: Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single-agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential.

Background: Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase- (COX-2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX-2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity.

Methods: Patients with resectable (T3-4, N1-2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions.

Results: Thirty-two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%-50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%-89%) and sphincter-sparing surgery (SSS): 56% (95% CI: 38%-74%). Common grade >3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease-free survival and overall survival (OS) were 84% (95% CI: 65%-93%) and 94% (95% CI: 77%-98%), respectively.

Conclusion: Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%-78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.
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http://dx.doi.org/10.1634/theoncologist.2017-0474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759821PMC
January 2018

INST OX-05-024: first line gemcitabine, oxaliplatin, and erlotinib for primary hepatocellular carcinoma and bile duct cancers: a multicenter Phase II trial.

Cancer Med 2017 Sep 11;6(9):2042-2051. Epub 2017 Aug 11.

Division of hematology/oncology, Department of medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression-free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.
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http://dx.doi.org/10.1002/cam4.1138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603839PMC
September 2017

Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with Hepatocellular Carcinoma: INST 08-20.

Oncologist 2017 10 7;22(10):1158-e116. Epub 2017 Jul 7.

Department of Hematology/oncology, University of New Mexico, Albuquerque, New Mexico, USA.

Lessons Learned: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn.

Background: Sorafenib is the currently approved first-line treatment for hepatocellular carcinoma (HCC). Capecitabine has antitumor activity in hepatobiliary cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and survival.

Methods: Patients with advanced HCC ineligible for locoregional therapy, Eastern Cooperative Oncology Group performance status of ≤2, Child-Pugh class A or B-7 cirrhosis, hemoglobin ≥8.5 g/dL, platelets ≥50,000/μL, absolute neutrophil count (ANC) ≥1,500 cells/μL, and serum creatinine of ≤2.0 mg/dL were recruited. All subjects received a combination of sorafenib and capecitabine, on a 14-day 7-days on 7-days off schedule. The primary end point was safety and secondary end points were overall survival (OS) and disease control rate.

Results: A total of 15 out of 47 patients met inclusion criteria. Median age was 64 years (56-79) and 77% were male. With a median follow-up of 12 months, median OS was 12.7 months (95% confidence interval [CI], 8.5-23.4). Disease control rate was 77% (complete response 8%, partial response 8%, and stable disease 61%). Common adverse events were as follows: (a) thrombocytopenia (64%); (b) anemia (14%); (c) hypophosphatemia (21%); (d) hypomagnesemia (14%); (e) hyperbilirubinemia (21%); (f) increased aspartate transaminase (AST) (14%); (g) hand-foot syndrome (21%); and (h) deep vein thrombosis (21%).

Conclusion: At tolerable doses, the combination of sorafenib and capecitabine seems an active and safe palliative treatment for HCC in class A and B-7 patients with cirrhosis. The small sample size does not allow comparison with single-agent sorafenib.
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http://dx.doi.org/10.1634/theoncologist.2017-0168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634773PMC
October 2017

Aggressive lymphoma presenting as dysphagia: A rare cause of dysphagia.

Clin Case Rep 2017 05 13;5(5):555-558. Epub 2017 Mar 13.

Department of Internal Medicine MSC10 5550 University of New Mexico Albuquerque New Mexico 87131 USA.

Diffuse large B-cell lymphoma (DLBCL) can involve the esophagus from local spread, distant metastasis and very rarely can also be the primary site. Once DLBCL is diagnosed, caution should be exercised in further evaluation for local treatments of sites like adnexal masses as was seen in this case; sometimes it is DLBCL at atypical sites.
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http://dx.doi.org/10.1002/ccr3.848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412793PMC
May 2017

An antivascular vaccine to boost self-immunity and strike the tumor.

Proc Natl Acad Sci U S A 2017 04 11;114(16):E3164-E3165. Epub 2017 Apr 11.

University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87106;

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http://dx.doi.org/10.1073/pnas.1701452114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402401PMC
April 2017

Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin in the treatment of secondary hemophagocytic lymphohistiocytosis with classical Hodgkin lymphoma: a case report and review of the literature.

J Med Case Rep 2016 Dec 20;10(1):365. Epub 2016 Dec 20.

University of New Mexico Comprehensive Cancer Center, 1201 Camino de Salud NE, Room 3618, 87131, Albuquerque, NM, USA.

Background: Hemophagocytic lymphohistiocytosis is becoming an increasingly recognized disorder in adults. Classical Hodgkin lymphoma is a relatively uncommon etiology of hemophagocytic lymphohistiocytosis and may complicate treatment options. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin are discussed here as a treatment regimen.

Case Presentation: A 66-year-old Hispanic man previously in good health presented with a 1-month history of recurrent fevers, chills, and night sweats and a 3-week history of new onset jaundice. A bone marrow biopsy revealed a normocellular bone marrow with increased histiocytes with areas of hemophagocytic activity. He met five out of eight criteria for hemophagocytic lymphohistiocytosis diagnosis including fevers, pancytopenia, hemophagocytosis, ferritin of 23,292 ng/mL (>500 ng/mL), and soluble-CD25 of 15,330 pg/mL (>1033 pg/mL). A right cervical lymph node biopsy revealed CD15, CD30, MUM-1, and Epstein-Barr virus-encoded small ribonucleic acid-positive cells with morphologic findings of classical Hodgkin lymphoma, lymphocyte-rich subtype. He completed 2 weeks of hemophagocytic lymphohistiocytosis-directed therapy with etoposide and dexamethasone, but then was switched to rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin due to minimal improvement in his pancytopenia and hepatic impairment. He completed one full cycle of rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin with notable improvement in serial hepatic function panels and had an undetectable Epstein-Barr virus viral load. However, he eventually died due to complications of Enterococcus faecalis bacteremia and colonic microperforation in the setting of persistent pancytopenia.

Conclusions: This case discusses the challenges facing treatment of adult malignancy-associated hemophagocytic lymphohistiocytosis. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin may be a viable option for patients with secondary hemophagocytic lymphohistiocytosis and Hodgkin lymphoma who cannot tolerate standard therapies due to hepatic impairment. Targeted therapy and immunotherapy are promising new areas of developing treatments.
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http://dx.doi.org/10.1186/s13256-016-1143-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175318PMC
December 2016

Recent Advances in Immunotherapy in Metastatic NSCLC.

Front Oncol 2016 14;6:239. Epub 2016 Nov 14.

Department of Internal Medicine, Division of Hematology/Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM, USA; Molecular Therapeutics Program, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

Non-small cell lung cancer (NSCLC) is one of most common malignancies and the leading cause of cancer deaths worldwide. Despite advances in targeted therapies, majority of NSCLC patients do not have targetable genomic alterations. Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and several breakthroughs in immunotherapies have led to rapid expansion of this new treatment modality in NSCLC with recent FDA approvals of programed death receptor-1 inhibitors, such as nivolumab and pembrolizumab. Here, we review promising immunotherapeutic approaches in metastatic NSCLC, including checkpoint inhibitors, agents with other mechanisms of action, and immunotherapy combinations with other drugs. With advent of immunotherapy, therapeutic options in metastatic NSCLC are rapidly expanding with the hope to further expand life expectancy in metastatic lung cancer.
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http://dx.doi.org/10.3389/fonc.2016.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107578PMC
November 2016

The role of local ablative therapy in oligometastatic non-small-cell lung cancer: hype or hope.

Future Oncol 2016 Dec 28;12(23):2713-2727. Epub 2016 Jul 28.

Department of Internal Medicine, Division of Hematology/Oncology, University of New Mexico School of Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.

In recent years, the emergence of the oligometastatic state has called into question whether patients found to have a limited or low metastatic tumor burden may benefit from locally ablative therapy (LAT). In the past two decades, stereotactic body radiation therapy has been increasingly used to safely deliver LAT and provide high local control in nonoperable non-small-cell lung cancer patients. Mostly retrospective analyses suggest that using LAT for oligometastatic disease in non-small-cell lung cancer offers excellent local control and may provide an improvement in progression-free survival. Any meaningful improvement in cancer-specific survival remains debatable. We examine the role of integrating LAT in this patient population and the rationale behind its use in combination with targeted therapy and immunotherapy.
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http://dx.doi.org/10.2217/fon-2016-0219DOI Listing
December 2016

Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC.

Front Oncol 2016 4;6:112. Epub 2016 May 4.

Department of Internal Medicine, Division of Hematology/Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM, USA; Cancer Genetics, Epigenetics, and Genomics Research Program, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.
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http://dx.doi.org/10.3389/fonc.2016.00112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854869PMC
May 2016

Isodicentric Philadelphia chromosome: an uncommon chromosomal abnormality in the chronic phase of chronic myeloid leukemia (CML).

Clin Case Rep 2016 Jan 19;4(1):43-5. Epub 2015 Nov 19.

Department of Medicine University of New Mexico Albuquerque New Mexico.

An isodicentric Philadelphia chromosome is an uncommon finding previously described as a secondary chromosomal abnormality in accelerated- or blast-phase of chronic myeloid leukemia (CML) with resistance to imatinib mesylate or dasatinib. Here, we present a case with idic(Ph) chromosome identified at initial diagnosis in a patient with chronic-phase CML.
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http://dx.doi.org/10.1002/ccr3.444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706395PMC
January 2016

Overview for the histone codes for DNA repair.

Prog Mol Biol Transl Sci 2012 ;110:207-27

Department of Medicine, University of Florida, Gainesville, Florida, USA.

DNA damage occurs continuously as a result of various factors-intracellular metabolism, replication, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy. If left unrepaired, this damage could result in changes or mutations within the cell genomic material. There are a number of different pathways that the cell can utilize to repair these DNA breaks. However, it is of utmost interest to know how the DNA damage is signaled to the various DNA pathways. As DNA damage occurs within the chromatin, we postulate that modifications of histones are important for signaling the position of DNA damage, recruiting the DNA repair proteins to the site of damage, and creating an open structure such that the repair proteins can access the site of damage. We discuss the modifications that occur on the histones and the manner in which they relate to the type of damage that has occurred as well as the DNA repair pathways that are activated.
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http://dx.doi.org/10.1016/B978-0-12-387665-2.00008-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039077PMC
September 2013

Training in clinical research in India.

Indian J Community Med 2010 Jul;35(3):446

University College of Medical Sciences, New Delhi, India. E-mail:

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http://dx.doi.org/10.4103/0970-0218.69289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963895PMC
July 2010
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