scholarly journals Is Host Metabolism the Missing Link to Improving Cancer Outcomes?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2338
Author(s):  
Christopher M. Wright ◽  
Anuradha A. Shastri ◽  
Emily Bongiorno ◽  
Ajay Palagani ◽  
Ulrich Rodeck ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Tumor Cells ◽  
Treatment Options ◽  
Detailed Knowledge ◽  
Pharmacological Agents ◽  
Molecular Alterations ◽  
Number Of Patients ◽  
Disease Site ◽  
New Treatment ◽  
The Impact

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are being targeted for therapeutic gain. In this review, we argue that—to optimize the impact of old and new treatment options—we need to take account of an epidemic that occurs independently of—but has major impact on—the development and treatment of malignant diseases. This is the rapidly increasing number of patients with excess weight and its’ attendant metabolic consequences, commonly described as metabolic syndrome. It is well established that patients with altered metabolism manifesting as obesity, metabolic syndrome and chronic inflammation have an increased incidence of cancer. Here, we focus on evidence that these patients also respond differently to cancer therapy including radiation and provide a perspective how exercise, diet or pharmacological agents may be harnessed to improve therapeutic responses in this patient population.

scholarly journals Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders

2020 ◽  
Vol 21 (3) ◽  
pp. 991 ◽  
Author(s):  
Angelina Vladimirovna Pakhomova ◽  
Vladimir Evgenievich Nebolsin ◽  
Olga Victorovna Pershina ◽  
Vyacheslav Andreevich Krupin ◽  
Lubov Alexandrovna Sandrikina ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Dicarboxylic Acid ◽  
Metabolic Disorders ◽  
Biological Effects ◽  
Treatment Options ◽  
The Metabolic Syndrome ◽  
Pancreatic Stem Cells ◽  
The Impact

In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.

scholarly journals IDH1 Targeting as a New Potential Option for Intrahepatic Cholangiocarcinoma Treatment—Current State and Future Perspectives

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3754
Author(s):  
Fabiana Crispo ◽  
Michele Pietrafesa ◽  
Valentina Condelli ◽  
Francesca Maddalena ◽  
Giuseppina Bruno ◽  
...  
Keyword(s):  
Treatment Options ◽  
Point Mutations ◽  
Genetic Alterations ◽  
Idh1 Mutation ◽  
Primary Malignancy ◽  
Pharmacological Agents ◽  
Molecular Alterations ◽  
Starting Point ◽  
Metabolic Remodeling ◽  
Mutant Idh1

Cholangiocarcinoma is a primary malignancy of the biliary tract characterized by late and unspecific symptoms, unfavorable prognosis, and few treatment options. The advent of next-generation sequencing has revealed potential targetable or actionable molecular alterations in biliary tumors. Among several identified genetic alterations, the IDH1 mutation is arousing interest due to its role in epigenetic and metabolic remodeling. Indeed, some IDH1 point mutations induce widespread epigenetic alterations by means of a gain-of-function of the enzyme, which becomes able to produce the oncometabolite 2-hydroxyglutarate, with inhibitory activity on α-ketoglutarate-dependent enzymes, such as DNA and histone demethylases. Thus, its accumulation produces changes in the expression of several key genes involved in cell differentiation and survival. At present, small-molecule inhibitors of IDH1 mutated enzyme are under investigation in preclinical and clinical phases as promising innovative treatments for IDH1-mutated intrahepatic cholangiocarcinomas. This review examines the molecular rationale and the results of preclinical and early-phase studies on novel pharmacological agents targeting mutant IDH1 in cholangiocarcinoma patients. Contextually, it will offer a starting point for discussion on combined therapies with metabolic and epigenetic drugs, to provide molecular support to target the interplay between metabolism and epigenetics, two hallmarks of cancer onset and progression.

Circulating tumor cells (CTCs) as a predictor of metastatic disease in patients with biochemical recurrence (BR) of prostate cancer with equivocal scan results.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 239-239
Author(s):  
Jeanny B. Aragon-Ching ◽  
Samuel J. Simmens ◽  
Steven R. Patierno ◽  
Robert S. Siegel
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Bone Biopsy ◽  
Treatment Options ◽  
Primary Treatment ◽  
Testosterone Levels ◽  
Number Of Patients ◽  
Bone Scans

239 Background: Staging for BR is challenging since the yield of computed tomography (CT) and bone scans are low, especially in patients with low prostate specific antigens (PSA) levels. We examined the utility of circulating tumor cells (CTCs) to predict metastatic disease in a cohort of patients who presented with BR (Aragon-Ching, et. al. ASCO GU 2011;abstr 60). Methods: 33 pts enrolled from May 2010 to September 2011 with BR, defined as patients (pts) who have undergone primary treatment with PSA rise to >/= 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy, were included. PSA doubling time (PSADT), scan results, Gleason scores, age, testosterone levels were all obtained. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. BR patients with equivocal CT and/or bone scan results who were biopsiable and consentable underwent bone biopsy to confirm metastatic disease. Results: The median age for 33 patients was 71 y/o (range: 51 – 91), median PSA of 1.7 ng/mL (range 0.2 – 65.8), testosterone levels of 315.5 ng/dL (range: 31 – 727), Gleason score of 7, hemoglobin of 13.78 g/dL, BMI of 27.72 and alkaline phosphatase of 68 IU/L. Prostatectomy was the primary treatment in 23 pts, radiotherapy in 9 pts and Cyberknife in 1 pt. Median PSADT varied between 0.35 to 55.2 months. Only a small number of patients had either biopsy confirmed metastatic disease (n=2) or detectable CTC (n=3). Both of the 2 patients with metastatic disease had detectable CTC (sensitivity = 1.00, 95% CI: .34, 1.00). For the patients without signs or confirmation of metastatic disease, 30/31 had no detectable CTC (specificity = .97, 95% CI: .84, .99). Conclusions: While most pts with BR have negative blood CTCs, patients with detectable CTCs and equivocal findings on scans should raise suspicion and prompt a search for metastatic disease, given increasing available treatment options for metastatic prostate cancer. However, the limited number of patients may preclude reliable statistical evaluation of CTCs in this population. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.

The impact of the COVID-19 pandemic on oncology clinical trial recruitment in an Irish cancer center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18756-e18756
Author(s):  
Ronan Andrew McLaughlin ◽  
Valerie Madigan ◽  
Maureen O'Grady ◽  
Thamir Andrew Mahgoub ◽  
Roshni Andrew Kalachand ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Informed Consent ◽  
Treatment Options ◽  
Cancer Clinical Trial ◽  
University Hospital ◽  
Cancer Center ◽  
Cancer Clinical Trials ◽  
Number Of Patients ◽  
The Impact

e18756 Background: The COVID-19 pandemic has created unprecedented disruptions to cancer clinical trial research across the world due to a temporary global suspension of patients’ recruitment to cancer clinical trials. Access to clinical trials permits better treatment options and best clinical practice standards for patients with cancer. We present the impact of the COVID-19 pandemic on cancer clinical trial activity at the Cancer Clinical Trials Unit (CCTU) at the Mid-Western Cancer Centre, University Hospital Limerick (UHL). Over the last 4 years 28 clinical trials, both interventional and translational, have opened here, across a variety of primary disease sites, with 5 trials opened in 2017, 11 in 2018, 7 in 2019 but only 2 in the first 10 months of 2020 until 3 further trials were opened in December. Methods: CCTU records were reviewed to identify the number of patients screened and consented to participate in cancer clinical trials at UHL in 2020, which were compared directly with corresponding numbers for 2019. Results: In 2019, 17 clinical trials were open and recruiting at the CCTU, UHL. During 2020, 19 trials were recruiting although during the 1st surge of the COVID-19 pandemic recruitment was essentially suspended and CCTU staff were redeployed throughout the hospital. 1st Six months 2020 vs 2019 In the six months from January 2020 until the end of June 2020, 99 patients were screened and only 15 (15.2%) signed informed consent to participate in a cancer clinical trial. When these figures are directly compared with the first six months of 2019, there is a 33% reduction in patients screened for participation (147 vs 99) and a 60% reduction in patients consented (37 vs 15) to clinical trials. 12 Months 2020 vs 2019 In total during 2019, 376 patients were screened for inclusion to participate and 49 (13%) patients signed informed consent to participate in a clinical trial within CCTU at UHL. In 2020, 914 patients were screened for participation with 51 patients consented to participate (5.6%). The majority (45/51 (88%)) of patients consented to cancer clinical trials in 2020 at the CCTU, UHL were recruited to translational based studies and only 6 (12%) consented to interventional studies compared with 2019 when 30/49 (61%) consented to translational and 30/49 (39%) to interventional studies. Conclusions: During the COVID-19 pandemic, the percentage of patients consented to participation in a clinical trial reduced significantly, as compared to the previous year (5.6% vs 13%). Fewer interventional studies have recruited patients during 2020. As we enter the third surge of COVID-19 infections in Ireland, we must continue to monitor and identify effective strategies to navigate the ever-changing situation for cancer clinical trials, in an attempt to maintain access to high quality cancer clinical trial opportunities for our patients.

Bendamustine Replaces Chlorambucil As “Standard of Care” in the Treatment of Elderly Patients with Chronic Lymphocytic Leukemia in German Hematology Outpatient Centres

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4605-4605
Author(s):  
Wolfgang Ulrich Knauf ◽  
Wolfgang Abenhardt ◽  
Arnd Nusch ◽  
Renate Grugel ◽  
Norbert Marschner
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
Real Life ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Line Treatment ◽  
Clinical Registry ◽  
Systemic Treatments ◽  
New Treatment ◽  
The Impact

Abstract Abstract 4605 Introduction With the FDA and EMA approval of Bendamustine and Rituximab new treatment options have recently become available to patients (pts) with chronic lymphocytic leukemia (CLL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 420 pts received systemic 1st-line treatment for CLL. 65% of pts are male, mean age at time of primary diagnosis was 66 years (yrs) and at start of therapy 69 yrs. Tumor stage was 20% Binet A, 35% Binet B and 45% Binet C. 68% of pts (n=285) were diagnosed with at least one comorbidity, mainly hypertension (37%) or diabetes (15%); the average Charlson Comorbity Index of 0.7 indicates that overall pts have few comorbities. Rituximab is part of the 1st-line treatment in 82% (n=345) of pts with CLL. Bendamustine is part of the 1st-line treatment in 59% (n=247) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 51%, n=213). Further 7% (n=28) receive Bendamustin as monotherapy. Fludarabine is part of the 1st-line treatment in 31% (n=132) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 25%, n=103), as monotherapy (4%, n=15) or in combination with Cyclophosphamide (FC, 1%, n=6). Chlorambucil is part of the 1st-line treatment in 7% (n=31) of pts with CLL. It is applied as monotherapy (4%, n=15) or in combination with Rituximab (2%, n=10). Pts receiving BR, FCR or Chlorambucil differ. Pts characteristics indicate that BR and Chlorambucil are applied preferably in elderly pts (mean 70.1 (BR) vs. 75.7 (Chlorambucil) vs. 63.4 (FCR) yrs). Also, BR is given preferably in advanced stages of the disease as compared to FCR (Binet C 49% vs. 34%). The use of BR has increased from 41% in 2009 to 57% in 2011, while the use of FCR has decreased from 33% in 2009 to 17% in 2011. Of all pts with CLL in the TLN, 181 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 76% (n=137) of pts with CLL. Bendamustine is part of the 2nd-line treatment in 66% (n=120) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 56%, n=101). Further 10% (n=18) receive Bendamustin as monotherapy. Fludarabine is part of the 2nd-line treatment in 20% (n=37) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 10%, n=18), as monotherapy (5%, n=9) or in combination with Cyclophosphamide (FC, 3%, n=5). Chlorambucil is part of the 2nd-line treatment in 4% (n=7) of pts with CLL. It is mostly applied in combination with Rituximab (2%, n=4). Conclusion Rituximab and Bendamustine are the most frequently used drugs for the treatment of CLL in German hematology outpatient centres. The use or BR has significantly increased since 2009. In contrast, the use of FCR has decreased and only a minority of pts receive Chlorambucil. This indicates that in Germany Chlorambucil is no longer considered the “standard of care” for elderly pts with CLL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of these new treatment options on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances

2021 ◽  
Vol 14 (4) ◽  
pp. 316
Author(s):  
Valentina Tateo ◽  
Lisa Manuzzi ◽  
Claudia Parisi ◽  
Andrea De Giglio ◽  
Davide Campana ◽  
...  
Keyword(s):  
Treatment Options ◽  
Biological Characterization ◽  
First Line ◽  
Molecular Alterations ◽  
Platinum Based Chemotherapy ◽  
New Treatment ◽  
Clinical Advances ◽  
Biological Differences ◽  
Thymic Tumors

Thymic tumors are a group of rare mediastinal malignancies that include three different histological subtypes with completely different clinical behavior: the thymic carcinomas, the thymomas, and the rarest thymic neuroendocrine tumors. Nowadays, few therapeutic options are available for relapsed and refractory thymic tumors after a first-line platinum-based chemotherapy. In the last years, the deepening of knowledge on thymus’ biological characterization has opened possibilities for new treatment options. Several clinical trials have been conducted, the majority with disappointing results mainly due to inaccurate patient selection, but recently some encouraging results have been presented. In this review, we summarize the molecular alterations observed in thymic tumors, underlying the great biological differences among the different histology, and the promising targeted therapies for the future.

scholarly journals Evaluation of the impact of CXCR4, ССR10 chemokine receptor expression in tumor tissue on relapse free survival in colon cancer patients

2019 ◽  
Vol 9 (1) ◽  
pp. 16-21
Author(s):  
R. V. Orlova ◽  
A. K. Ivanova ◽  
G. A. Raskin ◽  
S. I. Kutukova ◽  
A. V. Androsova
Keyword(s):  
Colon Cancer ◽  
Chemokine Receptors ◽  
Tumor Tissue ◽  
Treatment Options ◽  
Receptor Expression ◽  
Relapse Free Survival ◽  
Free Survival ◽  
New Treatment ◽  
The Impact

Considering a rise in colon cancer rates, searching for new treatment options remains highly relevant for this patient cohort. Determination of chemokine receptors in tumor tissue may become an additional prognostic tool that can be used for planning adjuvant therapy.

Metabolic Syndrome is a Risk Factor for Post-Operative Adhesions: Need for Novel Treatment Strategies

2018 ◽  
Vol 51 (01) ◽  
pp. 35-41 ◽  
Author(s):  
Yair Pilpel ◽  
Guy Pines ◽  
Andreas Birkenfeld ◽  
Stefan Bornstein ◽  
Rafael Miller
Keyword(s):  
Metabolic Syndrome ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Postoperative Adhesions ◽  
Invasive Procedures ◽  
Novel Treatment ◽  
Number Of Patients ◽  
Wide Range ◽  
Novel Treatment Strategies

AbstractMetabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.

scholarly journals The genetic basis of intradural spinal tumors and its impact on clinical treatment

2015 ◽  
Vol 39 (2) ◽  
pp. E3 ◽  
Author(s):  
Michael Karsy ◽  
Jian Guan ◽  
Walavan Sivakumar ◽  
Jayson A. Neil ◽  
Meic H. Schmidt ◽  
...  
Keyword(s):  
Treatment Options ◽  
Cancer Recurrence ◽  
Genetic Alterations ◽  
Spinal Tumors ◽  
Therapeutic Effects ◽  
Low Grade ◽  
Primary Therapy ◽  
Targeted Interventions ◽  
Molecular Alterations ◽  
The Impact

Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.

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