The International Journal of Medical Students, a Platform for Medical Student Research Worldwide

N/

Drug Delivery Approaches for the Treatment of Cervical Cancer

Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods

C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma

C1013G/CXCR4 actúa como una mutación activadora en la WM que conduce a un mayor creci-miento tumoral y como un inductor de resistencia a los medicamentos. BMS936564/MDX1338, un nuevo moAb anti-CXCR4, se dirige con éxito a las células WM, ya sean mutadas en C1013G/CXCR4 o de tipo salvaje. El receptor de quimiocinas C-X-C tipo 4 (CXCR4) desempeña un papel crucial en la modulación del tráfico celular de células madre hematopoyéticas y células B clonales. Se examinaron 418 pacientes con trastornos linfoproliferativos de células B y se describió la presencia de verrugas C1013G/CXCR4, hipogammaglobulinemia, infecciones y mutaciones asociadas a mielocatexis en el 28,2 % (37/131) de los pacientes con linfoma linfoplasmocítico (macroglobulinemia de Walden-ström [WM]), ausente o presente en solo el 7 % de otros linfomas de células B. La caracterización funcional in vivo demuestra su papel activador en las células WM, como lo demuestra la im-portante proliferación tumoral y la diseminación a los órganos extramedulares, lo que conduce a la progresión de la enfermedad y a la disminución de la supervivencia. El uso de un anticuerpo monoclonal anti-CXCR4 condujo a una reducción significativa del tumor en un modelo de WM C1013G/CXCR4, mientras que se observó resistencia a los fármacos en las células WM mutadas expuestas a la tirosina quinasa de Bruton, a la diana de rapamicina en mamíferos y a los inhibi-dores de la fosfatidilinositol 3-quinasa, pero no a los inhibidores del proteasoma. Estos hallazgos demuestran que C1013G/CXCR4 es una mutación activadora en la WM y respaldan su papel como regulador crítico de la patogénesis molecular de la WM y como una importante diana terapéutica. El Dr. Garcia-Sanz fue co-investigador senior en esta publicación que se hizo en colaboración con el Dana Farber Cancer Center de Boston y la Escuela de medicina de la Universidad de Harvard. La serie de casos que se analizó para detectar la mutación en MYD88 y CXCR4 tiene su origen en el Hospital Universitario de Salamanca, cuyo aportación deriva de la actividad asistencial e investigadora de Dr. García Sanz y el trabajo experimental de la licenciada Jiménez, y la super-visión del Dr. San Miguel. El resto de autores participó en el desarrollo de los estudios experi-mentales bajo la dirección ddl Dr. Roccaro y la supervisión de Irene Ghobrial.[EN]The C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in modulating cell trafficking in hematopoietic stem cells and clonal B cells. We screened 418 patients with B-cell lymphoproliferative disorders and described the presence of the C1013G/CXCR4 warts, hypogammaglobulinemia, infections, and myelokathexis–associated mutation in 28.2% (37/131) of patients with lymphoplasmacytic lymphoma (Waldenström macroglobulinemia [WM]), being either absent or present in only 7% of other B-cell lymphomas. In vivo functional characterization demonstrates its activating role in WM cells, as demonstrated by significant tumor proliferation and dissemination to extramedullary organs, leading to disease progression and decreased survival. The use of a monoclonal antibody anti-CXCR4 led to significant tumor reduction in a C1013G/CXCR4 WM model, whereas drug resistance was observed in mutated WM cells exposed to Bruton's tyrosine kinase, mammalian target of rapamycin, and phosphatidylinositol 3-kinase inhibitors, but not proteasome inhibitors. These findings demonstrate that C1013G/CXCR4 is an activating mutation in WM and support its role as a critical regulator of WM molecular pathogenesis and as an important therapeutic target.Dana Farber Cancer Center de Boston Hospital Universitario de SalamancaHospital Universitario de Salamanc

Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed “screening and diagnostic” algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN

Full-endoscopic removal of third ventricular colloid cysts: technique, results, and limitations

IntroductionColloid cysts (CCs) are rare benign lesions that usually arise from the roof of the third ventricle. They may present with obstructive hydrocephalus and cause sudden death. Treatment options include ventriculoperitoneal shunting, cyst aspiration, and cyst resection microscopically or endoscopically. This study aims to report and discuss the full-endoscopic technique for removing colloid cysts.Materials and methodsA 25°-angled neuroendoscope with an internal working channel diameter of 3.1 mm and a length of 122 mm is used. The authors described the technique of resecting a colloid cyst by a full-endoscopic procedure and evaluated the surgical, clinical, and radiological results.ResultsTwenty-one consecutive patients underwent an operation with a transfrontal full-endoscopic approach. The swiveling technique (grasping the cyst wall and rotational movements) was used for CC resection. Of these patients, 11 were female, and ten were male (mean age, 41 years). The most frequent initial symptom was a headache. The mean cyst diameter was 13.9 mm. Thirteen patients had hydrocephalus at admission, and one needed shunting after cyst resection. Seventeen patients (81%) underwent total resection; 3 (14%), subtotal resection; and 1 (5%), partial resection. There was no mortality; one patient had permanent hemiplegia, and one had meningitis. The mean follow-up period was 14 months.ConclusionEven though microscopic resection of cysts has been widely used as a gold standard, successful endoscopic removal has been described recently with lower complication rates. Applying angled endoscopy with different techniques is essential for total resection. Our study is the first case series to show the outcomes of the swiveling technique with low recurrence and complication rates

The Role of HER2 Status in the Biliary Tract Cancers

Despite recent advances, biliary tract cancer (BTC) is traditionally known as being hard to treat with a poor prognosis. Recent state-of-the-art genomic technologies such as next-generation sequencing (NGS) revolutionized cancer management and shed light on the genomic landscape of BTCs. There are ongoing clinical trials to assess the efficacy of HER2-blocking antibodies or drug conjugates in BTCs with HER2 amplifications. However, HER2 amplifications may not be the sole eligibility factor for these clinical trials. In this review, we aimed to comprehensively examine the role of somatic HER2 alterations and amplifications in patient stratification and provide an overview of the current state of ongoing clinical trials

Therapeutic Targeting of Alternative RNA Splicing in Gastrointestinal Malignancies and Other Cancers

Recent comprehensive genomic studies including single-cell RNA sequencing and characterization have revealed multiple processes by which protein-coding and noncoding RNA processing are dysregulated in many cancers. More specifically, the abnormal regulation of mRNA and precursor mRNA (pre-mRNA) processing, which includes the removal of introns by splicing, is frequently altered in tumors, producing multiple different isoforms and diversifying protein expression. These alterations in RNA processing result in numerous cancer-specific mRNAs and pathogenically spliced events that generate altered levels of normal proteins or proteins with new functions, leading to the activation of oncogenes or the inactivation of tumor suppressor genes. Abnormally spliced pre-mRNAs are also associated with resistance to cancer treatment, and certain cancers are highly sensitive to the pharmacological inhibition of splicing. The discovery of these alterations in RNA processing has not only provided new insights into cancer pathogenesis but identified novel therapeutic vulnerabilities and therapeutic opportunities in targeting these aberrations in various ways (e.g., small molecules, splice-switching oligonucleotides (SSOs), and protein therapies) to modulate alternative RNA splicing or other RNA processing and modification mechanisms. Some of these strategies are currently progressing toward clinical development or are already in clinical trials. Additionally, tumor-specific neoantigens produced from these pathogenically spliced events and other abnormal RNA processes provide a potentially extensive source of tumor-specific therapeutic antigens (TAs) for targeted cancer immunotherapy. Moreover, a better understanding of the molecular mechanisms associated with aberrant RNA processes and the biological impact they play might provide insights into cancer initiation, progression, and metastasis. Our goal is to highlight key alternative RNA splicing and processing mechanisms and their roles in cancer pathophysiology as well as emerging therapeutic alternative splicing targets in cancer, particularly in gastrointestinal (GI) malignancies