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Article ; Online: T-Cell Subsets as Potential Biomarkers for Hepatobiliary Cancers and Selection of Immunotherapy Regimens as a Treatment Strategy.

Kumar-Sinha, Chandan / Sahai, Vaibhav

Journal of the National Comprehensive Cancer Network : JNCCN

2022 Volume 20, Issue 2, Page(s) 203–214

Abstract: Patients with advanced hepatocellular or biliary cancers have a dismal prognosis with limited efficacy from standard systemic therapies. The benefit of precision medicine has so far been limited to a subset of biliary cancers, including FGFR ... ...

Abstract	Patients with advanced hepatocellular or biliary cancers have a dismal prognosis with limited efficacy from standard systemic therapies. The benefit of precision medicine has so far been limited to a subset of biliary cancers, including FGFR rearrangements; hotspot mutations in IDH1/2, BRAF, and BRCA1/2; and other rare alterations. In contrast, hepatocellular carcinoma, an inflammation-driven cancer with an immune-infiltrated microenvironment, provides a promising opportunity for immunotherapy, compared with the highly desmoplastic immune desert or excluded stromal microenvironment in biliary cancers. The immune contexture in hepatobiliary cancers is mostly immunosuppressive, protumorigenic, and exhausted, which together with low tumor mutation burden and decreased neoantigens provides challenges for immunotherapy. A better understanding of the spatiotemporal profile of T cells within the tumor microenvironment and the dynamic interplay of immune modulators in the context of standard or experimental therapies is crucial to define additional markers of response and design evidence-based combinatorial regimens. This review considers recent literature in this area and highlights promising leads and emerging trends.
MeSH term(s)	Biomarkers, Tumor/genetics ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/therapy ; Humans ; Immunotherapy ; Liver Neoplasms/genetics ; Liver Neoplasms/therapy ; T-Lymphocyte Subsets ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2021.7097
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Article ; Online: Defining cancer growth beyond the mitotic index.

Kumar-Sinha, Chandan / Chinnaiyan, Arul M

Nature cell biology

2022 Volume 24, Issue 3, Page(s) 285–287

MeSH term(s)	Cell Proliferation ; Humans ; Mitotic Index ; Neoplasms
Language	English
Publishing date	2022-03-15
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-022-00862-7
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Article ; Online: Reply to "Contextualizing racial associations in prostate cancer to expose structural causes".

Karan, Dev / Wick, Jo / Dubey, Seema / Kumar-Sinha, Chandan / Siddiqui, Javed / Kunju, Lakshmi P / Iczkowski, Kenneth A / Chinnaiyan, Arul M

Cancer

2023 Volume 130, Issue 4, Page(s) 647–648

MeSH term(s)	Humans ; Male ; Prostatic Neoplasms ; Racial Groups ; Causality
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35167
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Article ; Online: Racial differences in serum chemokines in prostate cancer patients.

Karan, Dev / Wick, Jo / Dubey, Seema / Kumar-Sinha, Chandan / Siddiqui, Javed / Kunju, Lakshmi P / Iczkowski, Kenneth A / Chinnaiyan, Arul M

Cancer

2023 Volume 129, Issue 23, Page(s) 3783–3789

Abstract: Background: This study aimed to understand the differential levels of inflammatory chemokines in association with higher prostate cancer incidence and mortality in African American (AA) men than in Caucasians (CA).: Methods: The authors used a ... ...

Abstract	Background: This study aimed to understand the differential levels of inflammatory chemokines in association with higher prostate cancer incidence and mortality in African American (AA) men than in Caucasians (CA). Methods: The authors used a chemokine assay to simultaneously measure 40 chemokines and cytokines levels in the serum of preoperative prostate cancer patients and healthy controls of AA and CA races. Selected chemokines (CXCL2, CXCL5, and CCL23) serum level was validated in 211 serum samples from prostate cancer patients and healthy controls. Differential expression of CXCL5 and CCL23 was analyzed using immunohistochemistry in a representative cohort of prostate tumor tissues of AA and CA races. Results: Race-specific comparisons from 211 serum samples showed significantly higher levels of CXCL2 (control: 3104.0 pg/mL vs. cancer: 2451.0 pg/mL) and CXCL5 (control: 5189.0 pg/mL vs. cancer: 5459.0 pg/mL) in AA men than in CAs (CXCL2; control: 1155.0 pg/mL vs. cancer: 889.3 pg/mL, and CXCL5; control: 1183.0 pg/mL vs. cancer: 977.5 pg/mL). CCL23 differed significantly within and between the races with a lower level in AA cancer cases (454.5 vs. 966.6 pg/mL) than healthy controls (740.5 vs. 1263.0 pg/mL). Patient age, prostate-specific antigen, or Gleason scores were not significantly associated with these chemokines. Immunostaining for CXCL5 and CCL23 in a representative cohort of archival prostate tissues displayed significantly higher CXCL5 in prostate tumors than in adjacent benign tissues, whereas CCL23 was nondetectable in most of the analyzed tumor tissues. Conclusion: Lower levels of CCL23 in AA prostate cancer patient sera and tumor tissues and high CXCL2 and CXCL5 may contribute to aggressive prostate cancer, as often seen in AA men. The disproportionate levels of serum chemokines associated with race warrant further exploration to improve equitability in precision oncology to benefit prostate cancer patients.
MeSH term(s)	Male ; Humans ; Race Factors ; Precision Medicine ; Prostatic Neoplasms/pathology ; Chemokines ; Prostate-Specific Antigen
Chemical Substances	Chemokines ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35012
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Article ; Online: Case Study: Systematic Detection and Prioritization of Gene Fusions in Cancer by RNA-Seq: A DIY Toolkit.

Vats, Pankaj / Chinnaiyan, Arul M / Kumar-Sinha, Chandan

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2079, Page(s) 69–79

Abstract: RNA-seq provides an efficient and sensitive methodology to identify fusion transcripts in cancer tissues. Chimeric reads mapping across two different genes represent potential gene fusions. Various methodologies have been implemented in the detection of ... ...

Abstract	RNA-seq provides an efficient and sensitive methodology to identify fusion transcripts in cancer tissues. Chimeric reads mapping across two different genes represent potential gene fusions. Various methodologies have been implemented in the detection of gene fusions by RNA-seq. Here we describe a general methodology used in processing and filtering of RNA-seq data, followed by filtering of multiple varieties of artifacts to nominate potentially relevant gene fusions. Functional relevance of gene fusions is assessed based on the predicted domain architecture of the putative fusion proteins.
MeSH term(s)	Algorithms ; Computational Biology/methods ; Databases, Genetic ; Gene Fusion ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Molecular Sequence Annotation ; Neoplasms/genetics ; RNA-Seq ; Sequence Analysis, RNA ; Software ; Workflow
Language	English
Publishing date	2019-11-11
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9904-0_5
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Article ; Online: Lorlatinib for the Treatment of ALK Fusion-Positive Infant-Type Hemispheric Glioma: A Case Report.

Greenwell, Alyssa M / Baughan, Scott / Altinok, Deniz / Marupudi, Neena I / Kupsky, William / Kumar-Sinha, Chandan / Gorsi, Hamza S

JCO precision oncology

2022 Volume 6, Page(s) e2200255

MeSH term(s)	Humans ; Lactams, Macrocyclic/therapeutic use ; Pyrazoles/therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics ; Glioma/drug therapy
Chemical Substances	lorlatinib (OSP71S83EU) ; Lactams, Macrocyclic ; Pyrazoles ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Case Reports ; Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.22.00255
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Article ; Online: Identification of Novel PGR-NR4A3 Fusion in Extraskeletal Myxoid Chondrosarcoma and Resultant Patient Benefit From Tamoxifen Therapy.

Wilbur, H Catherine / Robinson, Dan R / Wu, Yi-Mi / Kumar-Sinha, Chandan / Chinnaiyan, Arul M / Chugh, Rashmi

JCO precision oncology

2022 Volume 6, Page(s) e2200039

MeSH term(s)	Chondrosarcoma/drug therapy ; DNA-Binding Proteins/genetics ; Gene Fusion ; Humans ; Neoplasms, Connective and Soft Tissue/drug therapy ; Receptors, Steroid/genetics ; Receptors, Thyroid Hormone/genetics ; Tamoxifen/therapeutic use
Chemical Substances	DNA-Binding Proteins ; NR4A3 protein, human ; Receptors, Steroid ; Receptors, Thyroid Hormone ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2022-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.22.00039
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Article ; Online: Breast carcinoma presenting with upper limb lymphedema - A rare case.

Jha, Chandan Kumar / Sinha, Upasna / Sinha, Mainak / Singh, Prashant Kumar

Breast disease

2023 Volume 42, Issue 1, Page(s) 395–399

Abstract: Lymphedema (LE) in a breast cancer patient usually results from axillary lymph node dissection, sentinel lymph node biopsy, and/or axillary radiotherapy. Although lymphatic obstruction and consequent LE can occur due to axillary lymph node involvement, ... ...

Abstract	Lymphedema (LE) in a breast cancer patient usually results from axillary lymph node dissection, sentinel lymph node biopsy, and/or axillary radiotherapy. Although lymphatic obstruction and consequent LE can occur due to axillary lymph node involvement, such presentation in breast cancer patients has rarely been reported. This report describes the case of a 50-year-old lady with right breast carcinoma who presented with right upper limb lymphedema. Surprisingly, she did not have any bulky axillary lymphadenopathy that could have accounted for lymphedema of the upper limb, but a suspicious breast mass was present on clinical examination. Diagnosis of breast cancer on clinical examination can be challenging in such patients due to breast edema and careful imaging of the breast and axilla with appropriate imaging tools (mammogram, ultrasound, MRI, PET mammography) should be resorted to before excluding malignancy. Lymphoscintigraphy confirmed the findings of lymphedema in the right upper limb and revealed uptake in the epitrochlear lymph nodes of the contralateral limb suggesting that she might had pre-existing widespread "subclinical lymphedema" which presented as "clinical lymphedema" in right upper limb after axillary lymph node/lymphatic involvement by right breast carcinoma.
MeSH term(s)	Female ; Humans ; Middle Aged ; Breast Neoplasms/complications ; Upper Extremity ; Lymphedema/diagnostic imaging ; Lymphedema/etiology ; Breast ; Axilla ; Carcinoma
Language	English
Publishing date	2023-12-18
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	639267-2
ISSN	1558-1551 ; 0888-6008
ISSN (online)	1558-1551
ISSN	0888-6008
DOI	10.3233/BD-230022
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Article ; Online: Ultrasound-guided interventions in primary carpal tunnel syndrome: perineural injection to thread carpal tunnel release.

Kumar, Nishith / Chandan, Shishir Kumar / Jalan, Divesh / Sinha, Skand / Jaiswal, Binita / Singh, Dharmendra Kumar

The British journal of radiology

2023 Volume 96, Issue 1150, Page(s) 20230552

Abstract: Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, is compression of the median nerve deep to transverse carpal ligament at wrist. Ultrasonography and electrophysiological study are complementary in the diagnosis and grading of CTS in ... ...

Abstract	Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, is compression of the median nerve deep to transverse carpal ligament at wrist. Ultrasonography and electrophysiological study are complementary in the diagnosis and grading of CTS in appropriate clinical settings. The initial management of patients with CTS is conservative with medical therapy and splinting. However, surgical interventions are indicated in patients in whom medical management has failed. With evolution of the concept of safe zone on ultrasonography and identification of the sonoanatomical landmarks of carpal tunnel in greater detail, Ultrasonography-guided interventions are safer and preferred over surgical management in CTS. The primary ultrasonography-guided interventions include perineural injection, perineural hydrodissection and ultrasonography-guided release of transverse carpal ligament. This review article presents the principles of ultrasonography-guided perineural injection, perineural hydrodissection in CTS, the merits and demerits of injectant used in perineural injection/ hydrodissection, and percutaneous ultrasonography-guided thread release of transverse carpal ligament utilizing the concept of safe zone of the ultrasonography-guided interventions for CTS.
MeSH term(s)	Humans ; Carpal Tunnel Syndrome/diagnostic imaging ; Carpal Tunnel Syndrome/surgery ; Ultrasonography, Interventional ; Median Nerve/diagnostic imaging ; Median Nerve/surgery ; Ultrasonography ; Wrist Joint
Language	English
Publishing date	2023-09-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20230552
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Article ; Online: Pathogenic ATM and BAP1 germline mutations in a case of early-onset, familial sarcomatoid renal cancer.

Bell, Hannah N / Kumar-Sinha, Chandan / Mannan, Rahul / Zakalik, Dana / Zhang, Yuping / Mehra, Rohit / Jagtap, Deepa / Dhanasekaran, Saravana M / Vaishampayan, Ulka

Cold Spring Harbor molecular case studies

2022 Volume 8, Issue 3

Abstract: Metastatic renal cell carcinoma (RCC) remains an incurable malignancy, despite recent advances in systemic therapies. Genetic syndromes associated with kidney cancer account for only 5%-8% of all diagnosed kidney malignancies, and genetic predispositions ...

Abstract	Metastatic renal cell carcinoma (RCC) remains an incurable malignancy, despite recent advances in systemic therapies. Genetic syndromes associated with kidney cancer account for only 5%-8% of all diagnosed kidney malignancies, and genetic predispositions to kidney cancer predisposition are still being studied. Genomic testing for kidney cancer is useful for disease molecular subtyping but provides minimal therapeutic information. Understanding how aberrations drive RCC development and how their contextual influences, such as chromosome loss, genome instability, and DNA methylation changes, may alter therapeutic response is of importance. We report the case of a 36-yr-old female with aggressive, metastatic RCC and a significant family history of cancer, including RCC. This patient harbors a novel, pathogenic, germline ATM mutation along with a rare germline variant of unknown significance in the
MeSH term(s)	Adult ; Ataxia Telangiectasia Mutated Proteins/genetics ; Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/genetics ; Female ; Genomic Instability ; Germ-Line Mutation/genetics ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Sarcoma ; Soft Tissue Neoplasms ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	BAP1 protein, human ; Tumor Suppressor Proteins ; ATM protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2835759-0
ISSN	2373-2873 ; 2373-2873
ISSN (online)	2373-2873
ISSN	2373-2873
DOI	10.1101/mcs.a006203
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