Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern ...immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.
Objectives
Treatment for advanced renal cell carcinoma (RCC) has become increasingly more complex over the last several years. Objective 1 is to which treatment option is immunotherapy, targeted ...therapy, or the combination of immunotherapy with targeted therapy the best for patients? Objective 2 is to study which regimens with the highest chance of cure/durable response and what is the optimal sequence in advanced RCC.
Materials and methods
Between 2016 and 2018, 6 adult patients admitted to our institute with RCC were reviewed. Clinical information, treatment and outcomes were retrieved for further analysis. This applies to all risk groups as determined by the International Metastatic RCC Database Consortium criteria. We have intended to provide the reader with a comprehensive and authoritative review of the broad subject of RCC.
Results
Immunotherapy-based regimens and the functioning of various growth-and survival-promoting kinases, specifically, receptor-associated tyrosine kinases have dramatically changed the treatment landscape of advanced RCC. Recent phase III trials have demonstrated a survival benefit for front-line ipilimumab plus nivolumab therapy, and immune checkpoint inhibition plus anti-vascular endothelial growth factor combination therapy in metastatic clear-cell RCC.
Conclusion
In renal cell carcinoma, rapid and successful drug development has resulted in multiple treatment options, requiring careful decision making for individual patients and have emphasized how newly developed therapies work.
The DNA damaging revolution Cetin, Bulent; Wabl, Chiara A.; Gumusay, Ozge
Critical reviews in oncology/hematology,
December 2020, 2020-12-00, Letnik:
156
Journal Article
Recenzirano
Display omitted
•PARP inhibitors are promising treatments for cancers with BRCA mutations and in other cancers with defective homologous recombination.•Inhibition of ATR/CHK1 signaling is a unique ...strategy to overcome PARP inhibitor resistance.•Novel biomarkers are potential candidates to predict response to PARP inhibitors.
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that plays a critical role in the repair of single-strand DNA damage via the base excision repair pathway. PARP inhibitors have substantial single-agent antitumor activity by inducing synthetic lethality. They have also emerged as promising anticancer targeted therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. PARP inhibition produces single-strand DNA breaks, which may be repaired by homologous recombination, a process partially dependent on BRCA1 and BRCA2. The PARP inhibitors olaparib, veliparib, talazoparib, niraparib, and rucaparib have predominantly been studied in patients with breast or ovarian cancers associated with deleterious germline mutations in BRCA1 and BRCA2. Ongoing clinical trials are evaluating the role of PARP inhibitors alone and in combination with other therapies, including selective inhibitors against key targets involved in the DNA damage response. In this review we summarize the use of PARP inhibitors in various tumor types, as well as possible approaches for overcoming resistance to PARP inhibitors.
Classic Kaposi's sarcoma: A review of 156 cases Cetin, Bulent; Aktas, Bilge; Bal, Oznur ...
Dermatologica Sinica,
December 2018, 2018-12-00, 2018-12-01, Letnik:
36, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Kaposi's sarcoma (KS) is a reactive, multifocal, multicentric, angiogenic neoplastic proliferation that is thought to originate from endothelial cells that are infected with human herpesvirus-8 ...(HHV-8). This report examines a cohort of patients with classic Kaposi's sarcoma (KS) evaluated at the national institute of oncology over the 13-year period.
A retrospective analysis of 156 patients with classic KS, between January 2000 and November 2013, was performed. This study focused on the clinical presentation, staging, diagnosis, and treatment of classic KS.
One hundred fifty-six patients (median age 69 and 115 male) were enrolled into the study. Median age at diagnosis was 69 (range: 32–95 years). Male/female ratio was 2.80. The most common location was the lower limbs. There were 75 stage I patients (48.1%), 8 stage II patients (22.4%), 31 stage III patients (19.9%) and 15 stage IV patients (9.6%). Surgery was the most common local treatment method (43%). 44 patients (28.2%) received radiotherapy (RT) at diagnosis. Cytotoxic treatment with chemotherapy or interferon-α was administered in 57 patients. Visceral involvement was observed in 10 patients (lung: nine patients, liver: one patient) and bone metastasis occurred in two patients at relapse.
This study is one of the largest reported series. Further studies are required and it will be important to standardize the assessment of disease activity and clinical response.
Summary
Aim
The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model.
Methods
Eighteen Wistar albino rats were divided into three groups: ...experimental toxicity was induced with crizotinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively.
Results
Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas.
Conclusion
This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.
Surgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining ...cytotoxic chemotherapy with bevacizumab in this patient population.
We identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival.
Patients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4%) underwent additional surgery, while three patients (5.7%) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95% CI: 10.6-23.3 months) and 23 months for the surgery group (95% CI: 21.3-24.6 months; P = 0.322).
This study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.
The hydrodistillated essential oils and hexane extracts of two spice plants, Cymbocarpum erythraeum (DC.) Boiss. and Echinophora tenuifolia L. were analyzed by GC and GC-MS. C. erythraeum oil is rich ...in aliphatic aldehydes, alcohols and acids and (E)-2-decenal (26.1%), (E)-2-decen-1-ol (15.7%), (E)-2-dodecenal (13.2%) and decanal (7.8%) were the predominant components. However, ethyl palmitate (16.4%), 2-decenoic acid (14.1%) and (E)-2-dodecenal (5.2%) were the major components of the hexane extract of C. erythraeum. E. tenuifolia oil contained mainly methyl eugenol (53.0%), p-cymene (17.0%) and α-phellandrene (13.2%). The hexane extract displayed a different chemical composition, and n-tricosane (75.0%) and n-pentacosane (7.6%) were found to be the major compounds. The oils showed antimicrobial activity against various microorganisms and they were more active against the tested fungal species as compared with bacteria. The growths of important food-borne pathogens, Salmonella, Staphylococcus aureus and Escherichia coli were also inhibited by the oils. However, hexane extract of C. erythraeum was showed weak antibacterial activity against limited number of tested bacteria. The current results showed that the essential oils of C. erythraeumand E. tenuifolia can be used in food preservation.
The treatment landscape for advanced prostate cancer is evolving rapidly, with new agents and strategies, and more optimal use of existing therapies under constant development. Efforts were focused ...on better understanding of the biology of the disease.This effort has paved the way for a more contemporary and effective therapies to be developed. There are now 6 FDA-approved therapies that increase overall survival. These include the immunotherapy sipuleucel-T; the 2 androgen pathway inhibitors: abiraterone acetate and enzalutamide; 2 chemotherapy drugs: docetaxel and cabazitaxel; and the radionuclide: radium-223. Advanced prostate cancer may be one of the few cancers for which multiple chemotherapy and nonchemotherapy regimens are considered as standard. Several recently published clinical trials have demonstrated the suprising activity of chemotherapy-free strategies, and we should not be too eager to discount these ‘‘old-fashioned'' treatments. Optimal sequencing is still unclear because new therapies have proliferated so quickly that comparative data are limited. In this short communication, we identify current challenges and unmet needs in advanced prostate cancer and provide an overview of their respective clinical activity, while highlighting distinctions between therapies.
Investigation of the traditional cheeses and bringing them to the industry contributes to the development of dairy technology in terms of quality and diversity. For this purpose, traditional Turkish ...mouldy Civil cheese, which has a rich microbial diversity and is lovingly consumed, was studied and its yeast flora revealed. Samples were evaluated in terms of aerobic plate count, psychrotrophic bacteria, proteolytic bacteria, yeast, mould, coliform, enterococci, presumptive lactobacilli, presumptive lactococci, Staphylococcus aureus and Enterobacteriaceae counts. Seventy isolates were characterised by RAPD-PCR with M13 primer. Six diverse species were detected: Yarrowia lipolytica, Kluyveromyces marxianus, Pichia membranifaciens, Debaryomyces hansenii, Pichia fermentans and Candida zeylanoides. As a result, yeast diversity in mouldy Civil cheese may have an important role on development of characteristic blue cheese flavour and selected yeast strains could be used as adjunct culture to improve the quality of the final product.
Opinion statementThe treatment of renal cell carcinoma (RCC) is one of the great success stories in the field of oncology, which was revolutionized with the development of therapies aimed at ...disrupting crucial pathways. Tumor biology of RCC has provided insight into the disease through elucidation of the role of vascular endothelial growth-factor (VEGF) and the mammalian target of rapamycin (mTOR). Targeted agents against VEGF and mTOR, as well as agents targeting relevant immunomodulatory pathways, have shown clinical benefit for advanced disease. The targeted agents are highly effective in achieving a response and survival, particularly in high-risk patients. These include the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) axitinib and cabozantinib, and programmed cell death 1 protein (PD-1) immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab. There is a wealth of evidence investigating different therapeutic options and combinations for first-line treatment of advanced RCC including the CheckMate 214 study, KEYNOTE-426, JAVELIN Renal 101, and CheckMate 9ER. Dual ICI and combination agents targeting the programmed cell death protein 1/programmed cell death protein ligand 1 (PD1/PDL1) and VEGF, began to demonstrate superiority over previously accepted standards in advanced clear-cell RCC. Data from a number of clinical studies are available to help physicians with evidence-based decisions for the sequence of second-line and future treatments for patients with progressive RCC. In this review, we focus on essentials for clinicians treating patients with clear-cell RCC.
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