Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines

Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.

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Chemopreventive Role of Phytoconstituents in Breast Cancer: An Integration Therapy

Current Bioactive Compounds ◽

10.2174/1573407218666211230141836 ◽

2021 ◽

Vol 18 ◽

Author(s):

Priya Bhatt ◽

Mehul Patel ◽

Aashka Thakkar ◽

Umang Shah ◽

Ashish Patel ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Modern Medicine ◽

Chemotherapeutic Agents ◽

Primary Objective ◽

Health Concern ◽

Ongoing Research ◽

Significant Public Health

As we enter into the era of modern medicine, breast cancer remains a significant public health concern that has a noteworthy global impact in developed and developing countries. The modern era has seen an increase in the knowledge of the molecular mechanisms underlying cancer progression, leading to many anticancer drugs. The practice of curing certain diseases with the help of plant-derived compounds was one of the traditional methods. Phytochemicals and derivatives present in plants have shown a promising effect for improving efficiency in the treatment of cancer patients and reducing adverse reactions such as integration therapy with chemotherapeutic agents. The primary objective of this review is to compile ongoing research, preclinical studies, and clinical trials of some of the important phytochemicals. In recent years, increasing evidence from preclinical and clinical studies suggests that phytochemicals can favorably modulate several signaling pathways involved in cancer development and progression. Furthermore, phytoconstituents or plant-derived compounds show synergistic action against breast cancer when integrated with chemotherapy. Thus, the therapeutic potential of naturally occurring phytochemicals is of great interest as a part of integration therapy in cancer care. This review focuses on phytochemicals from quinones, terpenoids, alkaloids, polyphenols, steroidal lactones, and glycosides classes that help treat breast cancer. In addition, the phytochemicals act by various pharmacological mechanisms like carcinogen inactivation, inhibiting proliferation, cell cycle arrest, and apoptosis. Collectively, detailed information about specific classes of phytoconstituents along with their mechanism of action is mentioned in this review.

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Toxicity reduction of adenovirus mediated thymidine kinase gene therapy for ovarian cancer and subsequent combination with topoisomerase inhibitors: Design of a clinical phase I study

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86111-4 ◽

1998 ◽

Vol 5 (1) ◽

pp. 47A-47A ◽

Cited By ~ 1

Author(s):

X TONG ◽

D ENGEHAUSEN ◽

D SHINE ◽

I AGOULNIK ◽

T KIM ◽

...

Keyword(s):

Ovarian Cancer ◽

Gene Therapy ◽

Phase I ◽

Thymidine Kinase ◽

Phase I Study ◽

Thymidine Kinase Gene ◽

Topoisomerase Inhibitors ◽

Kinase Gene ◽

Clinical Phase ◽

Toxicity Reduction

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The Therapeutic Potential of Chemokines in the Treatment of Chemotherapy- Induced Peripheral Neuropathy

Current Drug Targets ◽

10.2174/1389450120666190906153652 ◽

2020 ◽

Vol 21 (3) ◽

pp. 288-301 ◽

Cited By ~ 5

Author(s):

Lin Zhou ◽

Luyao Ao ◽

Yunyi Yan ◽

Wanting Li ◽

Anqi Ye ◽

...

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Immune System ◽

Peripheral Neuropathy ◽

Immune Cell ◽

Therapeutic Potential ◽

Chemotherapeutic Agents ◽

Cell Trafficking ◽

Mediated Communication ◽

Novel Therapeutic Strategies

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.

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Evaluating the Use of Cyberinfrastructure in the Classroom to Enhance Product Dissection

Volume 3: 19th International Conference on Design Theory and Methodology; 1st International Conference on Micro- and Nanosystems; and 9th International Conference on Advanced Vehicle Tire Technologies, Parts A and B ◽

10.1115/detc2007-35549 ◽

2007 ◽

Cited By ~ 2

Author(s):

Matt Devendorf ◽

Kemper Lewis ◽

Timothy W. Simpson ◽

Robert B. Stone ◽

William C. Regli

Keyword(s):

Phase I ◽

High Impact ◽

Lessons Learned ◽

Digital Design ◽

Design Engineering ◽

National Scale ◽

Research Experiences ◽

Ongoing Research ◽

Information Tools ◽

Digital Environments

Recent cyberinfrastructure initiatives seek to create ubiquitous, comprehensive, interactive, and functionally complete digital environments that consist of people, data, information, tools, and instruments for research communities. With product dissection as our unifying theme, we are forging a cyberinfrastructure to support undergraduate design engineering education through CIBER-U: Cyber-Infrastructure-Based Engineering Repositories for Undergraduates. CIBER-U pairs two of the nation’s leading design repository developers with several active users and their students to realize a high-impact application of cyberinfrastructure in engineering undergraduate curricula involving freshmen through seniors. Specifically, CIBER-U combines product dissection activities at three universities with two digital design repositories, CAD modeling and animation, video, MediaWiki technology, multimedia, and undergraduate summer research experiences to enable cyberinfrastructure-based product dissection activities. Nearly 700 students have participated in the Phase I efforts of CIBER-U, which have focused primarily on generating, capturing, and storing data in two digital design repositories. Lessons learned from these efforts are presented from the students’ perspectives as well as that of the faculty in both engineering and computer science. The implications for implementing CIBER-U on a national scale are discussed along with ongoing research.

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KP1019, A New Redox-Active Anticancer Agent - Preclinical Development and Results of a Clinical Phase I Study in Tumor Patients

Chemistry & Biodiversity ◽

10.1002/cbdv.200890195 ◽

2008 ◽

Vol 5 (10) ◽

pp. 2140-2155 ◽

Cited By ~ 537

Author(s):

Christian G. Hartinger ◽

Michael A. Jakupec ◽

Stefanie Zorbas-Seifried ◽

Michael Groessl ◽

Alexander Egger ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Anticancer Agent ◽

Preclinical Development ◽

Tumor Patients ◽

Clinical Phase ◽

Redox Active

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Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

Frontiers in Endocrinology ◽

10.3389/fendo.2020.612396 ◽

2021 ◽

Vol 11 ◽

Author(s):

Codruţa Şoica ◽

Mirela Voicu ◽

Roxana Ghiulai ◽

Cristina Dehelean ◽

Roxana Racoviceanu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Treatment Options ◽

Active Role ◽

Structural Features ◽

Sex Hormone ◽

Ongoing Research ◽

New Treatment ◽

Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

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Studies on the choice of subjects in clinical phase I tests. With emphasison evaluation of tranaminase levels prior to testing. 2.

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics ◽

10.3999/jscpt.20.283 ◽

1989 ◽

Vol 20 (1) ◽

pp. 283-284

Author(s):

MINAE KOBAYASHI

Keyword(s):

Phase I ◽

Clinical Phase

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Safety and Effectiveness of Favipiravir for Novel Coronavirus (COVID-19): A Rapid Review of Available Evidence

Health Technology Assessment in Action ◽

10.18502/htaa.v4i1.5862 ◽

2021 ◽

Author(s):

Mohammadreza Mobinizadeh ◽

Morteza Arab-Zozani

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Therapeutic Potential ◽

Data Extraction ◽

Rapid Review ◽

Eligibility Criteria ◽

Clinical Trial Registration ◽

Registration System ◽

Novel Coronavirus ◽

First Time

Context: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared for the first time in December 2019 in Wuhan, China. Due to the lack of unified and integrated evidence for Favipiravir, this study was conducted to rapidly review the existing evidence to help evidence-based decision-making on the therapeutic potential of this drug in the treatment of COVID-19 patients. Evidence Acquisition: This study is a rapid Health Technology Assessment (HTA). By searching pertinent databases, the research team collected relevant articles and tried to create a policy guide through a thematic approach. This rapid review was done in four steps: (1) Searching for evidence through databases; (2) screening the evidence considering eligibility criteria; (3) data extraction; and (4) analyzing the data through thematic analysis. Results: After applying the inclusion criteria, four studies were finally found, including three review studies and a clinical trial that was temporarily removed by its publisher from the journal’s website. After searching the sources mentioned in the articles, two ongoing clinical trials were found in China. Also, by searching the clinical trial website, www.clinicaltrials.gov, five clinical trials were found in the search. The result of the search in the clinical trial registration system in Iran showed a study that is in the process of patient recruitment. A limited number of other articles were found, mostly in the form of reflections from physicians or researchers and letters to editors who have predicted the drug’s performance on SARS-CoV-2, which needs further clinical study to be approved. Conclusions: With the available evidence, it is not possible to make a definite conclusion about the safety and efficacy of Favipiravir in the treatment of patients with COVID-19.

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