scholarly journals Exploring the Role of Novel Medical Therapies for Aggressive Pituitary Tumors: A Review of the Literature—“Are We There Yet?”

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 308 ◽  
Author(s):  
Lydia S. Lamb ◽  
Hao-Wen Sim ◽  
Ann I. McCormack
Keyword(s):  
Checkpoint Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Pituitary Tumors ◽  
Vascular Endothelial ◽  
Review Of The Literature ◽  
Vegf Inhibitors ◽  
Multiple Recurrences ◽  
Endothelial Growth Factor ◽  
Pituitary Carcinomas

Aggressive pituitary tumors account for up to 10% of pituitary tumors and are characterized by resistance to medical treatment and multiple recurrences despite standard therapies, including surgery, radiotherapy, and chemotherapy. They are associated with increased morbidity and mortality, particularly pituitary carcinomas, which have mortality rates of up to 66% at 1 year after diagnosis. Novel targeted therapies under investigation include mammalian target of rapamycin (mTOR), tyrosine kinase, and vascular endothelial growth factor (VEGF) inhibitors. More recently, immune checkpoint inhibitors have been proposed as a potential treatment option for pituitary tumors. An increased understanding of the molecular pathogenesis of aggressive pituitary tumors is required to identify potential biomarkers and therapeutic targets. This review discusses novel approaches to the management of aggressive pituitary tumors and the role of molecular profiling.

scholarly journals A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 919
Author(s):  
Eun-mi Yu ◽  
Laura Linville ◽  
Matthew Rosenthal ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Vascular Endothelial ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Improved Outcomes ◽  
Immune Oncology ◽  
Endothelial Growth Factor

The use of checkpoint inhibitors in advanced and metastatic renal cell carcinomas (RCCs) has rapidly evolved over the past several years. While immune-oncology (IO) drug therapy has been successful at resulting in improved responses and survival, combination therapies with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors have further improved outcomes. This article reviews the landmark trials that have led to the approval of IO therapies, including the Checkmate 214 trial and combination IO/VEGF TKI therapies with Checkmate 9ER, CLEAR, and Keynote-426, and it includes a discussion on promising therapies moving in the future.

The role of genetic polymorphisms of the VEGF, COX2, MUC genes in the development of endometriosis-associated infertility

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 34-37 ◽  
Author(s):  
Natalia V Kulikova ◽  
Inna I Kovalenko ◽  
Dmitrii V Baibuz ◽  
Yanina A Lebedeva
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Genetic Factors ◽  
Vascular Endothelial ◽  
Review Of The Literature ◽  
Timely Manner ◽  
Ongoing Research ◽  
Main Work ◽  
Muc Genes ◽  
Endothelial Growth Factor

Endometriosis-associated infertility is an important medical and social problem, because affects up to 10% of women in the reproductive case, while even after treatment the pregnancy occurs in only one third of the patients. The etiology of endometriosis is still not precisely defined, despite ongoing research on this topic. In this review of the literature, we have tried to highlight the main work concerning the participation of immunological and genetic factors in the pathogenesis, and the role of vascular endothelial growth factor, mucins and cyclooxygenase-2 in more detail. Further studies of these pathogenetic manifestations of infertility in patients with endometriosis will make it possible to correct them in a timely manner, thereby increasing the chances of pregnancy.

scholarly journals CTIM-30. EFFICACY OF PEMBROLIZUMAB IN PATIENTS WITH PITUITARY CARCINOMA: RESULTS FROM A PHASE II STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii39-ii40
Author(s):  
Nazanin Majd ◽  
Steven Waguespack ◽  
Janku Filip ◽  
Siqing Fu ◽  
Marta Penas-Prado ◽  
...  
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Gene Mutations ◽  
Pituitary Tumors ◽  
Molecular Data ◽  
Pituitary Carcinoma ◽  
Msh6 Gene ◽  
Best Response ◽  
Pituitary Carcinomas

Abstract Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region that leads to debilitating symptoms and poor survival. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there is interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated four pituitary carcinoma patients with pembrolizumab as part of a phase II clinical trial (NCT02721732). Here, we present their clinical course and outcomes and correlate responses with available molecular data: hypermutation status, PD-L1 staining, tumor-infiltrating lymphocyte score, microsatellite status and tumor mutational burden. Patients 1 and 2, with heavily pretreated, refractory corticotroph pituitary carcinoma, had partial radiographic (60% and 32% per irRECIST, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his baseline tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor was not sampled after exposure to temozolomide, but prior somatic mutational testing was negative. Patient 3 (non-functioning corticotroph tumor) had a best response of stable disease for four months. Patient 4 (prolactin-secreting carcinoma) had progressive disease. The latter two patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. PD-L1 staining was negative in all tumors. TIL score was 2 in Patients 1 and 4, negative in Patient 3 and not available in Patient 2. All patients tolerated the treatment well with mild adverse events. Our study generates the hypothesis that an alkylating agent-induced hypermutator phenotype may be an indicator of response to CPIs in pituitary carcinomas. The role of CPI in treating patients with pituitary carcinoma and mechanisms of hypermutation in this population require further study.

scholarly journals VEGF modulation and renal effects: Case report and review of the literature

2019 ◽  
Vol 7 (27) ◽  
pp. 58-63
Author(s):  
Camilo Pena-Hernandez ◽  
Rubayat Rahman ◽  
Subhanudh Thavaraputta ◽  
Nishi Garg
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Tubular Structures ◽  
Review Of The Literature ◽  
Vegf Inhibitors ◽  
Essential Step ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Angiogenesis has been known for decades to be an essential step in cancer growth. Inrecent years, the vascular endothelial growth factor (VEGF) family was identified as a crucialstimulus (and product by tumors) for neovascularization, nutrition, oxygen delivery, andmetastatic dissemination; VEGF inhibition currently has an important role in cancer therapy.The development and increased use of VEGF inhibitors has led to the identification of sideeffects and renal complications. Vascular endothelial growth factor is produced by renalpodocytes to maintain a healthy endothelium, mesangium, and tubular structures. With thedisruption of nutritional processes in the kidney, there can be renal injury starting at the cellularlevel and referred to by some experts as anti-VEGF nephropathy (hypertension, thromboticmicroangiopathy, proteinuria, renal failure).Here we present the case of a man with renal cell carcinoma who was treated with surgicalresection and later started on sunitinib. He developed several acute and chronic medicalproblems, including some related to anti-VEGF toxicity.

scholarly journals Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study

2020 ◽  
Vol 8 (2) ◽  
pp. e001532
Author(s):  
Nazanin Majd ◽  
Steven G Waguespack ◽  
Filip Janku ◽  
Siqing Fu ◽  
Marta Penas-Prado ◽  
...  
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Alkylating Agents ◽  
Evaluation Criteria ◽  
Gene Mutations ◽  
Pituitary Tumors ◽  
Pituitary Carcinoma ◽  
Tumor Patient ◽  
Pituitary Carcinomas

Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there has been interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated 4 patients with pituitary carcinoma with pembrolizumab as part of a phase II clinical trial. Two patients (patients 1 and 2) with functioning corticotroph pituitary carcinomas (refractory to surgery, radiotherapy and chemotherapy) had partial radiographic (60% and 32% per Immune-Related Response Evaluation Criteria In Solid Tumors, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor after exposure to temozolomide was not sampled, but prior somatic mutational testing was negative. One patient with a non-functioning corticotroph tumor (patient 3) had a best response of stable disease for 4 months. One patient with a prolactin-secreting carcinoma (patient 4) had progressive disease. The latter 2 patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. Programmed death-ligand 1 staining was negative in all tumors. We report 2 cases of corticotroph pituitary carcinoma responsive to pembrolizumab after prior exposure to alkylating agents. The role of CPIs in treating patients with pituitary carcinoma, the relationship between tumor subtype and response to immunotherapy and mechanisms of hypermutation in this orphan disease require further study.Trial registration number: NCT02721732.

scholarly journals Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat’s Kidneys Induced by Hypoxic Stress

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094979
Author(s):  
Aliah R. Alshanwani ◽  
Sameerah Shaheen ◽  
Laila M. Faddah ◽  
Ahlam M. Alhusaini ◽  
Hanaa M. Ali ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Hemoglobin Concentration ◽  
Vascular Endothelial ◽  
Hsp 70 ◽  
Reactive Protein ◽  
Defensive Role ◽  
Factor Α ◽  
Endothelial Growth Factor

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

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