Real-world data of poly (ADP-ribose) polymerase inhibitor response in Japanese patients with ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors have been increasingly used in the treatment of ovarian cancer, with BRCA positivity and homologous recombination deficiency (HRD) being common biomarkers used for predicting their efficacy. However, given the limitations of these biomarkers, new ones need to be explored. METHODS: This retrospective study included 181 ovarian cancer patients who received olaparib or niraparib at two independent hospitals in Japan between May 2018 and December 2022. Clinical information and blood sampling data were collected. Patient characteristics, treatment history, and predictability of treatment duration based on blood data before treatment initiation were examined. RESULTS: High-grade serous carcinoma, BRCA positivity, HRD, and maintenance therapy after recurrence treatment were observed more frequently in the olaparib group than in the niraparib group. The most common reasons for treatment interruption were anemia, fatigue, and nausea in the olaparib group and thrombocytopenia in the niraparib group. Regarding response to olaparib treatment, complete response to the most recent treatment, maintenance therapy after the first chemotherapy, high-grade serous carcinoma, and germline BRCA positivity were observed significantly more frequently among responders than among non-responders. Furthermore, neutrophil counts were significantly higher among responders than among non-responders. CONCLUSIONS: Inflammation-related blood data, such as neutrophil count, obtained at the initial pre-treatment visit might serve as potential predictors for prolonged olaparib treatment. While this study offers valuable insights into potential indicators for prolonged olaparib treatment, it underscores the need for more expansive research to strengthen our understanding of PARP inhibitors and optimize treatment strategies in ovarian cancer.

Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

A randomised controlled trial of Pre-Operative Oncotype DX testing in early-stage breast cancer (PRE-DX study) - Study protocol.

BACKGROUND: The Oncotype DX® Breast Recurrence Score assay can guide recommendations made to patients with oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer regarding post-surgery adjuvant therapy. Standard practice is to order the test in the post-operative setting on a specimen from the excised invasive carcinoma. However, it has been shown to be technically possible to perform the test on the diagnostic core biopsy. By testing the diagnostic core biopsy in the pre-operative setting, the wait for excised invasive carcinoma Recurrence Score results could be reduced allowing patients to be more accurately counselled regarding their treatment pathway sooner with any adjuvant treatment recommendations expedited. This would allow for more efficient streaming of follow up appointments. The aim of this study is to compare the impact on the patient treatment pathway of performing the Oncotype DX® test on the diagnostic core biopsy pre-operatively (intervention) as opposed to the excised invasive carcinoma (control). METHODS AND ANALYSIS: This parallel group randomised controlled trial aims to recruit 330 newly diagnosed patients with grade 2 or grade 3, ER+, HER2-, invasive intermediate risk early-stage breast cancer. Participants will be randomised 2:1 to the preoperative testing of the diagnostic core biopsy compared to the post-operative testing of the excision specimen. The primary endpoint is number of clinical touchpoints between treating team and patient from initial approach until offer and prescription of the first adjuvant treatment. Secondary endpoints include time from diagnosis to offer and prescription of the first adjuvant treatment, patient-reported anxiety scores and health cost impact analysis collected at baseline, following the post-operative clinic and following the offer of adjuvant treatment, and number of alterations in treatment sequence from original planned surgical treatment to neoadjuvant therapy. TRIAL REGISTRATION: The study was registered on ISRCTN (ISRCTN14337451) on the 16th August 2022.

Clinical responses to vemurafenib in postoperative recurrence of papillary thyroid carcinoma with esophageal fistula: A case report.

BACKGROUND: While papillary thyroid carcinoma (PTC) generally exhibits a favorable prognosis post-surgery, the poorly differentiated subtype presents elevated rates of postoperative recurrence. Certain aggressive cases demonstrate invasive behavior, compromising adjacent structures and leading to a poor prognosis. This study delineates a unique case of postoperative PTC recurrence, complicated by esophageal fistula, that showed favorable outcomes following brief Vemurafenib treatment. PATIENT DESCRIPTION: A 64-year-old female patient underwent surgical resection for PTC, subsequently experiencing rapid tumor recurrence and development of an esophageal fistula. DIAGNOSIS: The patient was confirmed to have locally advanced PTC through intraoperative cytopathology. The cancer recurred postoperatively, culminating in the formation of an esophageal fistula. METHODS: The patient was administered Vemurafenib at a dosage of 960 mg twice daily following tumor recurrence. RESULTS: A 12-month regimen of targeted Vemurafenib therapy led to a substantial reduction in tumor size. Concurrently, the esophageal fistula underwent complete healing, facilitating successful removal of the gastrostomy tube. The tumor response was classified as stable disease. CONCLUSION SUBSECTIONS: Vemurafenib demonstrates potential as a targeted therapeutic strategy for recurrent PTC harboring the BRAFV600E mutation. This approach may effectively mitigate tumor dimensions and the associated risk of esophageal and tracheal fistulas.

[History and Perspective of Chemotherapy in Advanced Esophageal Cancer].

Advanced esophageal carcinoma is one of the diseases with a poor prognosis. CF(cisplatin plus 5-FU)therapy and taxanes( paclitaxel or docetaxel)were considered standard treatments for first- and second-line treatment of advanced esophageal carcinoma based on the results of phase Ⅱ trials, although no randomized controlled trials were conducted. Subsequently, anti-epidermal growth factor receptor(EGFR)inhibitors, which had shown efficacy in head and neck cancer and colorectal cancer, were developed but failed to prolong survival both first- and second-line treatment. Immune checkpoint inhibitors have shown efficacy as single agents or in combination with chemotherapy in a variety of cancers, including esophageal cancer, where the KEYNOTE-181 trial and the ATTRACTION-3 trial demonstrated that single-agent pembrolizumab and nivolumab extended survival versus chemotherapy, respectively. In addition, the KEYNOTE-590 trial and the CheckMate 648 trial showed that pembrolizumab plus CF therapy was superior to CF, and nivolumab plus CF therapy and nivolumab plus ipilimumab were superior to CF in advanced esophageal carcinoma. These combinations have become the standard of care for the first-line treatment of advanced esophageal cancer. Immune checkpoint inhibitors had prolonged survival, but the results are still unsatisfactory, and CF therapy combined with immune checkpoint inhibitors and novel agents is being investigated. This article reviews the history of chemotherapy in advanced or recurrent esophageal cancer and discusses future prospects.

Nasopharyngeal Carcinoma in Children, Current Treatment Approach.

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of pediatric NPC includes chemotherapy and radiotherapy. Most studies on the treatment of pediatric NPC are single-arm studies. With current treatment protocols survival rates for patients with nonmetastatic disease exceed 80%, although most children will have long-term treatment-related late effects. Efforts to reduce early and late toxicities include reduced radiotherapy doses in children with good responses to induction chemotherapy. Further studies are needed to evaluate the role of immunotherapy in both the primary setting and in children with progressive or relapsed disease. This review summarizes current clinical approaches to the treatment of pediatric NPC.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

Brain metastasis in a patient with BRCA2-mutated treatment-related neuroendocrine prostate carcinoma and long-term response to radiotherapy and Olaparib: A case report and literature review.

BACKGROUND: A new subtype of prostate cancer called treatment-related neuroendocrine prostate carcinoma (t-NEPC) was added to the revised World Health Organization classification of prostate cancer in 2022. t-NEPC cases are increasing, and there is no established standard treatment. METHODS: A 49-year-old male patient was referred to our department for dysuria. A rectal examination and a prostate biopsy revealed stony hardness and prostate adenocarcinoma, respectively. Imaging studies confirmed the presence of multiple bone and lymph node metastases. The patient was started on upfront treatment with androgen deprivation therapy and an androgen receptor signaling inhibitor, which resulted in a significant (>90%) decrease in prostate-specific antigen (PSA) levels. The patient experienced postrenal failure 6 months later, attributable to local disease progression. Concurrently, there was an elevation in neuron-specific enolase (NSE) levels and an enlargement of pelvic lymph node metastases, without PSA progression. RESULTS: Biopsy specimen for cancer genome profiling revealed deletion of BRCA 2 and PTEN, AR amplification, and the presence of the TMPRSS2-ERG fusion gene. Based on increased NSE and BRCA2 mutations, a diagnosis of t-NEPC with BRCA2 mutation was eventually made. The patient received docetaxel chemotherapy and pelvic radiotherapy. Subsequently, he was treated with olaparib. His NSE levels decreased, and he achieved a complete response (CR). However, 18 months following the olaparib administration, brain metastases appeared despite the absence of pelvic tumor relapse, and the patient's PSA levels remained low. Consequently, the patient underwent resection of the brain metastases using gamma knife and whole-brain radiotherapy but died approximately 3 months later. CONCLUSION SUBSECTIONS: Platinum-based chemotherapy is often administered for the treatment of t-NEPC, but there are few reports on the effectiveness of olaparib in patients with BRCA2 mutations. In a literature review, this case demonstrated the longest duration of effectiveness with olaparib alone without platinum-based chemotherapy. Additionally, the occurrence of relatively rare, fatal brain metastases in prostate cancer after a long period of CR suggests the necessity of regular brain imaging examinations.

A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.

BACKGROUND: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors. METHODS: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups. RESULTS: 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor. CONCLUSIONS: In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.

Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex against triple negative mammary carcinoma.

A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non­platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo. OVMI has been reported to generate cytotoxicity in human triple negative breast carcinoma cells, MDA-MB-231 as well as in mouse 4T1 cells by priming them for apoptosis. ROS-mediated, mitochondria-dependent as well as ER-stress-evoked apoptotic death seemed to be main operational hub guiding the cytotoxicity of OVMI in vitro. Moreover, OVMI has been noticed to elicit antimetastatic effect in vitro. Therapeutic application of OVMI has been extended on 4T1-based mammary tumor of female Balb/c mice, where it has been found to reduce tumor size, volume and restore general tissue architecture successfully to a great extent. Apart from that, OVMI has been documented to limit 4T1-based secondary pulmonary metastasis along with being non-toxic and biocompatible in vivo.

Tris-Functionalized Polyoxotungstovanadate-Mediated Antitumor Efficacy Involves Multiple Cell Death Pathways.

Polyoxometalates (POMs) are promising inorganic drug candidates for cancer chemotherapy. They are becoming attractive because of their easy accessibility and low cost. Herein, we report the synthesis and antitumor activity studies of four Lindqvist-type POMs with mixed-addenda atoms Na2[V4W2O16{(OCH2)3CR}] (R=-CH2OH, -CH3, -CH2CH3) and (Bu4N)2[V3W3{(OCH2)3CH2OOCCH2CH3}]. Compared with the current clinical applied antitumor drug 5-fluorouracil (5-FU) or Gemcitabine, analysis of MTT/CCK-8 assay, colony formation and wound healing assay revealed that the {V4W2} POMs had acceptable cytotoxicity in normal cells (293T) and significant inhibitory effects on cell proliferation and migration in three human tumor cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa), and human breast cancer cells (MCF-7). Interestingly, among the POMs analyzed, the therapeutic index (TI) of the {V4W2} POM with R= -CH2OH was relatively the most satisfactory. Thus, it was subsequently used for further studies. Flow cytometry analysis showed it prompted cellular apoptosis rate. qRT-PCR and Western blotting analysis indicated that multiple cell death pathways were activated including apoptosis, autophagy, necroptosis and pyroptosis during the POM-mediated antitumor process. In conclusion, our study shows that the polyoxotungstovanadate has great potential to be developed into a broad-spectrum antitumor chemotherapeutic drug.

Effect of waiting time for radiotherapy after last induction chemotherapy on prognosis of locally advanced nasopharyngeal carcinoma.

BACKGROUND: The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. METHODS: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. RESULTS: The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003-1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57-4.6), OS (HR = 2.55; 95%CI: 1.29-5.03), DMFS (HR = 3.07; 95%CI: 1.64-5.76) and LRFS (HR = 2.26; 95%CI: 1.21-4.21). CONCLUSION: The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.

Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression.

Cancer profoundly influences morbidity and fatality rates worldwide. Patients often have dismal prognoses despite recent improvements in cancer therapy regimens. However, potent biomolecules derived from natural sources, including medicinal and dietary plants, contain biological and pharmacological properties to prevent and treat various human malignancies. Capsaicin is a bioactive phytocompound present in red hot chili peppers. Capsaicin has demonstrated many biological effects, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic capabilities. This review highlights the cellular and molecular pathways through which capsaicin exhibits antineoplastic activities. Our work also depicts the synergistic anticancer properties of capsaicin in conjunction with other natural bioactive components and approved anticancer drugs. Capsaicin inhibits proliferation in various cancerous cells, and its antineoplastic actions in numerous in vitro and in vivo carcinoma models impact oncogenesis, tumor-promoting and suppressor genes, and associated signaling pathways. Capsaicin alone or combined with other phytocompounds or approved antineoplastic drugs triggers cell cycle progression arrest, generating reactive oxygen species and disrupting mitochondrial membrane integrity, ultimately stimulating caspases and promoting death. Furthermore, capsaicin alone or in combination can promote apoptosis in carcinoma cells by enhancing the p53 and c-Myc gene expressions. In conclusion, capsaicin alone or in combination can have enormous potential for cancer prevention and intervention, but further high-quality studies are needed to firmly establish the clinical efficacy of this phytocompound.

An open, multicenter, exploratory study of apatinib mesylate maintenance therapy for recurrent/metastatic head and neck squamous cell carcinoma (ChiCTR1800019375).

BACKGROUND: This study evaluated the efficacy of apatinib in maintenance therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). METHODS: Twenty-six patients from three centers were enrolled from November 2018 to September 2021. These patients received 2 weeks apatinib, administered at 250 mg qd. Then apatinib dose may be administered to 500 mg qd continuous in 4 weeks cycle if no patients experienced adverse reaction. Enrolled patients can receive a combination of radiotherapy or chemotherapy. The primary endpoints were progression-free survival (PFS), and secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), quality of life (QOL) score, and adverse drug reactions. RESULTS: Median PFS of all patients was 3.2 months (95% CI: 2.06-4.33). Median OS of all patients was 7.3 months (95% CI: 2.14-12.46). The DCR was 92.3%. The ORR was 30.8%. In univariate analysis, the results showed that ECOG score 0-1 (HR = 0.31, p = 0.006) and treated with apatinib for more than 60 days (HR = 0.31, p = 0.003) were independent prognostic indicators affecting PFS, and ECOG score 0-1 (HR = 0.40, p = 0.027) and moderately differentiated or highly differentiated (HR = 0.38, p = 0.048) were independent prognostic indicators of OS. The most common adverse events among treated subjects included hypertension (46.1%), fatigue (42.3%), and hand-foot syndrome (23.1%). There were only two cases (7.7%) of Grade III or above adverse reactions. CONCLUSIONS: Maintenance therapy with apatinib is an effective and well-tolerated regimen in patients with R/M HNSCC.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Exploring In-Silico, In-Vitro Antioxidant, and Cytotoxic Potential of Valerian wallichii by On Cervical Epithelial Carcinoma (HeLa) Cell Lines.

Traditional medicinal practices often utilize herbal remedies for treating various diseases. This study focuses on exploring the phytochemical constituents, in-silico, in-vitro antioxidant, and anticancer activities of Valerian wallichii root extracts on human cervical epithelial carcinoma (HeLa) cell lines. The molecular docking approach was employed to predict the ligand molecule's orientation within the receptor like Epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) using Schrodinger's GLIDE model. Among the selected phytocompounds, hesperidin exhibited promising inhibitory activity against EGFR (Epidermal Growth Factor Receptor) domain with -8.701 kcal/mol docking score and interactions with MET 769, ASP 831, ASP776, LEU694 and ASN818 residues as compared to standard doxorubicin with -7.6 kcal/mol docking score and interactions with ASP 831, ASN818 and ASP776 residues and further, various antioxidant activity was assessed and In-vitro anticancer activity against HeLa cell lines was evaluated by hydroalcoholic root extracts demonstrated antioxidant capacities, and selective cytotoxicity was observed, with IC50 : 45.759±0.42 µg/mL for the overall extract and IC50 : 30.245±0.58 µg/mL for the EAF fraction as compared to standard doxorubicin with IC50 : 25.9891±0.25 µg/mL, respectively. The present study concluded that Valerian wallichii L possesses potential human cervical epithelial carcinoma cell line inhibition properties based on the computer aided drug design models and in-vitro activity.

A pilot study investigating plasma pharmacokinetics and tolerance of oral capecitabine in carcinoma-bearing dogs.

BACKGROUND: Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. RESULTS: Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m[Formula: see text] by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC[Formula: see text] was 890 h[Formula: see text]ng/ml (range 750-1100 h[Formula: see text]ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. CONCLUSIONS: Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.

Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies.

BACKGROUND: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. METHODS: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug-drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. RESULTS: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3-|34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9-|81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1-NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). CONCLUSION: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. CLINICAL TRIAL INFORMATION: FIH study, NCT02564900; DDI study, NCT03383692.

Metronomic cyclophosphamide and metformin inhibited tumor growth and repopulated tumor-infiltrating lymphocytes in an experimental carcinoma model.

Metformin is a widely used antidiabetic biguanide. Retrospective data demonstrated the association of metformin use with survival benefit in multiple tumor types. Interest in repurposing metformin to treat cancer has not been translated into encouraging clinical benefit. In animal models, metformin activated cytotoxic T cells and exerted an immune-mediated anticancer effect. The current research was conducted to investigate the possible therapeutic benefit of metformin in combination with metronomic cyclophosphamide in an experimental cancer model. Ehrlich ascites carcinoma was injected into the subcutaneous tissue to induce solid tumors in syngeneic mice. Exponential solid tumor growth ensued and was effectively arrested with the administration of a cytotoxic dose of parenteral cyclophosphamide. Alternatively, oral metformin and continuous, low-dose cyclophosphamide significantly inhibited tumor growth relative to untreated mice. The drug combination was well tolerated. Histopathological examination of the tumor showed an increased number of tumor-infiltrating lymphocytes and enhanced expression of granzyme B by this drug combination. The current data suggests a potential role of metformin and metronomic chemotherapy that warrants further investigation.

Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway.

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.