Faculty Opinions recommendation of When pain gets stuck: the evolution of pain chronification and treatment resistance.

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

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Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

Current Cancer Drug Targets ◽

10.2174/1568009618666180102103959 ◽

2018 ◽

Vol 18 (10) ◽

pp. 967-978 ◽

Cited By ~ 8

Author(s):

Katarina Kalavska ◽

Vincenza Conteduca ◽

Ugo De Giorgi ◽

Michal Mego

Keyword(s):

Germ Cell ◽

Molecular Mechanisms ◽

Cisplatin Resistance ◽

Apoptotic Cell ◽

Germ Cell Tumors ◽

Treatment Resistance ◽

Experimental Models ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

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Assessment of Treatment Resistance via Questionnaire

10.1093/oxfordhb/9780195366877.013.0034 ◽

2009 ◽

Author(s):

Julia N. Perry

Keyword(s):

Treatment Resistance

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Inflammatory Neuropsychiatric Disorders and COVID-19 Neuroinflammation

Acta Neuropsychiatrica ◽

10.1017/neu.2021.13 ◽

2021 ◽

pp. 1-55

Author(s):

Siu Wa Tang ◽

Daiga Helmeste ◽

Brian Leonard

Keyword(s):

Immune Responses ◽

Clinical Management ◽

Neuronal Damage ◽

Treatment Resistance ◽

Neuropsychiatric Disorders ◽

Acute Stage ◽

Management Approach ◽

Neuropsychiatric Diseases ◽

Anti Inflammatory

Abstract Neuropsychiatric sequalae to COVID-19 infection are beginning to emerge, like previous Spanish influenza and SARS episodes. Streptococcal infection in pediatric patients causing OCD (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, wide-spread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long term specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favorable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease modifying therapies are increasingly being applied to neuropsychiatric diseases characterized by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

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Targeting obesity-related dysfunction in hormonally driven cancers

British Journal of Cancer ◽

10.1038/s41416-021-01393-y ◽

2021 ◽

Author(s):

Maria M. Rubinstein ◽

Kristy A. Brown ◽

Neil M. Iyengar

Keyword(s):

Cell Signalling ◽

Treatment Resistance ◽

Tumour Microenvironment ◽

Subsequent Increase ◽

Treatment And Prevention ◽

Cancer Pathogenesis ◽

Diet And Exercise ◽

Systemic Factors ◽

Tumour Vascularity ◽

Obesity And Cancer

AbstractObesity is a risk factor for at least 13 different types of cancer, many of which are hormonally driven, and is associated with increased cancer incidence and morbidity. Adult obesity rates are steadily increasing and a subsequent increase in cancer burden is anticipated. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adipokine, and aromatase signalling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumour vascularity and inflammation in the tumour microenvironment, which can support tumour development and growth. Trials investigating non-pharmacological approaches to target the mechanisms driving obesity-mediated cancer pathogenesis are emerging and are necessary to better appreciate the interplay between malignancy, adiposity, diet and exercise. Diet, exercise and bariatric surgery are potential strategies to reverse the cancer-promoting effects of obesity; trials of these interventions should be conducted in a scientifically rigorous manner with dose escalation and appropriate selection of tumour phenotypes and have cancer-related clinical and mechanistic endpoints. We are only beginning to understand the mechanisms by which obesity effects cell signalling and systemic factors that contribute to oncogenesis. As the rates of obesity and cancer increase, we must promote the development of non-pharmacological lifestyle trials for the treatment and prevention of malignancy.

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Personality Disorders and Their Relation to Treatment Outcomes in Cognitive Behavioural Therapy for Depression: A Systematic Review and Meta-analysis

Cognitive Therapy and Research ◽

10.1007/s10608-021-10203-x ◽

2021 ◽

Author(s):

Harry Banyard ◽

Alex J. Behn ◽

Jaime Delgadillo

Keyword(s):

Systematic Review ◽

Cognitive Behavioural Therapy ◽

Meta Analysis ◽

Treatment Resistance ◽

Behavioural Therapy ◽

Risk Of Bias ◽

Cognitive Behavioural ◽

Primary Focus ◽

Effect Of Pd ◽

Evidence Based Care

Abstract Background Previous reviews indicate that depressed patients with a comorbid personality disorder (PD) tend to benefit less from psychotherapies for depression and thus personality pathology needs to be the primary focus of treatment. This review specifically focused on studies of Cognitive Behavioural Therapy (CBT) for depression examining the influence of comorbid PD on post-treatment depression outcomes. Methods This was a systematic review and meta-analysis of studies identified through PubMed, PsychINFO, Web of Science, and Scopus. A review protocol was pre-registered in the PROSPERO database (CRD42019128590). Results Eleven eligible studies (N = 769) were included in a narrative synthesis, and ten (N = 690) provided sufficient data for inclusion in random effects meta-analysis. All studies were rated as having “low” or “moderate” risk of bias and there was no significant evidence of publication bias. A small pooled effect size indicated that patients with PD had marginally higher depression severity after CBT compared to patients without PD (g = 0.26, [95% CI: 0.10, 0.43], p = .002), but the effect was not significant in controlled trials (p = .075), studies with low risk of bias (p = .107) and studies that adjusted for intake severity (p = .827). Furthermore, PD cases showed symptomatic improvements across studies, particularly those with longer treatment durations (16–20 sessions). Conclusions The apparent effect of PD on depression outcomes is likely explained by higher intake severity rather than treatment resistance. Excluding these patients from evidence-based care for depression is unjustified, and adequately lengthy CBT should be routinely offered.

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Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13123038 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3038

Author(s):

Mickaël Burgy ◽

Aude Jehl ◽

Ombline Conrad ◽

Sophie Foppolo ◽

Véronique Bruban ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Cell Cycle Progression ◽

Locally Advanced ◽

Treatment Resistance ◽

Neck Squamous Cell Carcinoma ◽

Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

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