Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting Focal adhesion kinase (FAK) and the Transforming Growth Factor ß (TGF-ß) pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, ß-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

[Pulmonary involvement in idiopathic inflammatory myopathies]. / Pulmonale Beteiligung bei idiopathischen inflammatorischen Myopathien.

Idiopathic inflammatory myopathies are rare systemic diseases with different types of pulmonary manifestations depending on the underlying aetiology; here, interstitial lung diseases (ILD) are the most frequently found patterns depending on the underlying disorder. There is a lack of sufficient prospective studies on this heterogeneous group of patients, particularly in case of ILD being involved. The diagnosis is based upon guideline recommendations for ILD and requires a multidisciplinary discussion within a team with specific expertise in this field. Myositis specific antibodies and myositis associated antibodies form an essential part of the diagnostic tools and may also be associated with a certain phenotype or disease progression. Anti-t-RNA-synthetase antibodies (Anti-ARS) and anti-melanoma differentiation-associated gene 5 antibodies (MDA5) play an important clinical role for treatment the estimation of response and prognosis. The most common ILD patterns are nonspecific interstitial pneumonia (NSIP) and organising pneumonia (OP) or a mixed pattern of both. Treatment is based on systemic steroids and early initiation of other immunosuppressant drugs. Evidence for this is, however, sparse, since most of the studies having investigated treatment modalities are of retrospective nature, even though some new prospective data may be useful for the establishment of treatment pathways in the future.

[Treatment alternatives for amyopathic MDA5-positive dermatomyositis]. / Therapiealternativen bei amyopathischer MDA5-positiver Dermatomyositis.

We report a case of an atypical course of therapy in amyopathic MDA5-antibody-positive dermatomyositis with interstitial lung disease. Due to the poor prognosis, early therapy with cyclophosphamide followed by rituximab was carried out initially in addition to the administration of prednisolone. Due to therapy failure, treatment was switched to mycophenolate mofetil. This showed a surprisingly rapid positive course in terms of interstitial lung disease, skin manifestation, and general disease activity.

Clinical Outcomes of Intensity Modulated Proton Therapy Reirradiation for Gynecologic Malignancies.

Purpose: Pelvic reirradiation (re-RT) for patients with gynecologic cancers remains a challenge because of toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients with re-RT to the pelvis/abdomen with intensity modulated proton therapy (IMPT) for gynecologic cancers. Methods and Materials: We performed a retrospective analysis of all patients with gynecologic cancer treated at a single institution between 2015 and 2021 with IMPT re-RT. Patients were included for analysis if the IMPT plan had at least partial overlap with the treated volume of a previous radiation treatment. Results: A total of 29 patients were included for analysis, with 30 total courses of re-RT. The majority of patients had been treated previously with conventional fractionation to a median dose of 49.2 Gy (30-61.6 Gy). With a median follow-up of 23 months, 1-year local control was 83.5% and overall survival was 65.7%. Three patients (10%) developed acute and late grade 3 toxicity. One-year freedom from late grade 3+ toxicity was 96.3%. Conclusions: This is the first complete analysis of clinical outcomes for re-RT with IMPT for gynecologic malignancies. We demonstrate excellent local control and acceptable acute and late toxicity. IMPT should strongly be considered for treatments requiring re-RT for gynecologic malignancies.

Pathologic complete response (pCR) rates and outcomes after neoadjuvant chemoradiotherapy with proton or photon radiation for adenocarcinomas of the esophagus and gastroesophageal junction.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is associated with improved survival in patients treated for esophageal cancer. While proton beam therapy (PBT) has been demonstrated to reduce toxicities with nCRT, no data comparing pCR rates between modalities exist to date. We investigated pCR rates in patients with distal esophageal/GEJ adenocarcinomas undergoing trimodality therapy with nCRT-PBT or photon-based nCRT with the hypothesis that pathologic responses with PBT would be at least as high as with photon therapy. METHODS: A single-institutional review of patients with distal esophageal adenocarcinoma treated with trimodality therapy from 2015-2018 using PBT was completed. PBT patients were matched 1:2 to patients treated with photons. Chi square and two-sample t-tests were utilized to compare characteristics, and the Kaplan Meier method was used to estimate oncologic endpoints. RESULTS: Eighteen consecutive PBT patients were identified and compared to 36 photon patients. All patients received concurrent chemotherapy; 98% with carboplatin/paclitaxel. Most patients were male (91%) and White (89%); median age was 62 years (range, 31-76 years). Median radiation dose in both cohorts was 50.4 Gy (range, 41.4-50.4 Gy); all courses were delivered in 1.8Gy fractions. Age, gender and race were well balanced. Patients treated with PBT had a significantly higher pre-treatment nodal stage (N) and AJCC 7th edition stage grouping (P=0.02, P=0.03). Despite this, tumoral and nodal clearance and pCR rates were equivalent between cohorts (P=0.66, P=0.11, P=0.63, respectively). Overall pCR and individual primary and nodal clearance rates, overall survival (OS), locoregional control (LRC), and distant metastatic control did not significantly differ between modalities (all P>0.05). Major perioperative events were balanced; however, there were 5 (14%) perioperative deaths in the photon cohort compared to 0 (0%) in the proton cohort (P=0.06). CONCLUSIONS: The use of PBT in trimodality therapy for distal esophageal adenocarcinoma yields pCR rates comparable to photon radiation and historical controls. Pathologic responses and oncologic outcomes in this study did not differ significantly between modalities despite PBT patients having higher AJCC stages and nodal disease burdens.