Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy.

PURPOSE: Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients. METHODS: Patients at our institutions from 2005 to 2018, with BC who did not achieve complete response (pCR) after NAC were reviewed (IRB protocol STU- 052012-019). Data, including evidence of ASA use, and clinico-pathologic parameters were analyzed. Survival outcomes were obtained (Kaplan Meier analysis) and univariate (UVA) and multivariable (MVA) Cox proportional hazards regression analyses were performed. RESULTS: 637 did not achieve pCR (ypN+ = 422). 138 were ASA users. Median follow-up for the control and ASA group were 3.8 (IQR 2.2-6.3) and 3.8 (IQR 2.5-6.4) years, respectively. Majority were stage II/III. 387 were hormone receptor positive, 191 HER2 +, and 157 triple negative. On UVA, ASA use, PR status, pathologic and clinical stage showed significance for DMFS, and disease-free survival (DFS). On MVA, ASA use associated with improved 5-year DFS (p = .01, 87.0% vs 79.6%, adjusted HR = 0.48) and improved 5-year DMFS (p = .04, 92.8% vs 89.2%, adjusted HR = 0.57). In the ypN + patients, ASA use associated with improved 5-year DMFS (p = .008, 85.7% vs 70.7%, adjusted HR = 0.43) and DFS (p = .02, 86.8% vs 74.3%, adjusted HR = 0.48). CONCLUSION: For non-responders, particularly ypN + patients, ASA use associated with improved outcome. These hypotheses-generating results suggest for development of prospective clinical trials of augmented ASA use in selected very high-risk BC patients.

A novel technique for safe percutaneous biopsy of a petrous apex lesion.

Lesions within the skull base are the most challenging targets for percutaneous biopsy due to the likelihood of encountering a critical structure along any needle trajectory. Due to ICA proximity, the petrous apex is considered unsafe. We describe a novel percutaneous CT-guided approach for biopsying a petrous apex lesion via a contralateral mandibular condylar notch (subzygomatic approach). To our best knowledge, this approach has not been reported and can be safely employed with thorough planning.

Body Mass Index: A Reliable Predictor of Subcutaneous Fat Thickness and Needle Length for Ventral Gluteal Intramuscular Injections.

BACKGROUND: With rising prevalence of obesity, increasing number of gluteal injections would be expected to fail in intramuscular (IM) drug delivery. STUDY QUESTION: This study evaluated ventral gluteal fat thickness (VGT) on adult magnetic resonance imaging of pelvis and correlated it with the subjects' body mass index (BMI), weight, and height to establish evidence-based clinical estimates of individualized needle length and suitability of ventral gluteal site for IM injections. DESIGN: Retrospective review. STUDY DESIGN, MEASURES AND OUTCOMES: Three hundred fifty adult (224 women, 126 men) magnetic resonance imaging scans of pelvis were reviewed to measure the VGT as the distance between the skin and the nearest edge of the gluteus medius muscle at the recommended ventral gluteal injection site. VGT was correlated with BMI, weight, and height by multivariate analysis. RESULTS: Fifty-three (49 women, 4 men) subjects had VGT greater than 3.3 cm, and 146 (106 women, 40 men) subjects had VGT greater than 2.0 cm. The Pearson correlation coefficient between VGT and BMI was 0.82 for women and 0.81 for men. The difference between the VGT in men and women of comparable BMI was statistically significant (P < 0.001). BMI of 30 in women and 35 in men seem to be upper limits for successful ventral gluteal IM injections with 3.75-cm (1.5-inch) hypodermic needle. The expected failure rate of ventral gluteal IM delivery with the 3.75-cm needle is 71% in women with BMI >30, and 60% in men with BMI >35. CONCLUSION: BMI is reliably predictive of VGT in both men and women for selecting appropriate needle length for IM injections at this site. Standard needles would fail in IM delivery at this site in a considerable proportion of obese adults. Because of high prevalence of obesity in individuals with severe mental illness, our findings could significantly impact acute and maintenance therapy with injectable tranquillizers and antipsychotics.

A Large Cohort Study of 18F Fluoro-Deoxy-Glucose Uptake in Normal Spinal Cord: Quantitative Assessment of the Contamination From Adjacent Vertebral Marrow Uptake and Validity of Normalizing the Cord Uptake Against the Lumbar Thecal Sac.

PURPOSE: This study aimed (1) to assess the influence of age, sex, blood glucose, and body mass index on the F fluoro-deoxy-glucose (F-FDG) uptake in normal spinal cord; (2) to quantitatively evaluate contamination of the spinal cord SUVmax by the adjacent vertebral marrow activity; and (3) to investigate the validity of normalizing spinal cord SUVmax against lumbar thecal sac SUVmax. METHODS: Two hundred positron emission tomography-computed tomography examinations of subjects with normal spinal cord were retrospectively reviewed. SUVmax of spinal cord and vertebral body was obtained at C2, C5, T6, T12, and L3 levels. Pearson correlation coefficients (r) were obtained at each level between spinal cord SUVmax and vertebral marrow SUVmax, age, body mass index, and blood glucose. Cord to background ratio (CTB) was calculated as the ratio between SUVmax of spinal cord and SUVmax of L3 thecal sac. The coefficient of variation (CV) of spinal cord SUVmax was compared with the CV of CTB. RESULTS: Spinal cord SUVmax was highest at C2 (mean, 1.76) and lowest at T6 (mean, 1.37) with SD of 0.32 to 0.36 SUV. Sex (P > 0.45), age (r: -0.25 to -0.06), body mass index (r: 0.19 to 0.27), and blood glucose (r: -0.17 to 0.22) had no impact on the spinal cord SUVmax. A moderate to strong positive correlation (r: 0.66-0.80) was found between spinal cord SUVmax and the corresponding vertebral marrow SUVmax. The CV of CTB was greater (0.28-0.32) than the CV of spinal cord SUVmax (0.19-0.25) across all levels. CONCLUSIONS: Of the variables studied, only contamination from adjacent vertebral marrow activity significantly affected the SUVmax of spinal cord. This contamination should be corrected for when reporting spinal cord FDG uptake. Lumbar thecal sac is not a valid reference for normalizing spinal cord FDG uptake.

Hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: A single institution Indian experience.

BACKGROUND: Cytoreductive surgery followed by hyper- thermic intraperitoneal chemotherapy (HIPEC) has shown better oncological outcomes in peritoneal surface malignancies (PSM). We assessed the feasibility and perioperative outcomes of this procedure in Indian patients. METHODS: In this prospective observational study from February 2013 to April 2015, we included 56 patients (41 females, 73.2%) with PSM. They had a good performance status, were either treatment-naïve or previously treated by surgery and systemic chemotherapy. They underwent cytoreductive surgery followed by HIPEC using a hyperthermia pump, with the temperature at 42 °C for 30-90 minutes. The chemotherapy regimen was based on the primary malignancy. Perioperative outcome data were collected and analysed. We also analysed the short-term oncological outcomes. RESULTS: Our patients included those with peritoneum confined ovarian carcinoma (32, 57.1%), colorectal carcinoma (9, 16.1%), pseudomyxoma peritonei (7, 12.5%), meso- thelioma (2, 3.6%), gastric carcinoma (2, 3.6%) and others (4, 7.1%). The median duration of surgery including HIPEC was 9 hours and the median hospital stay was 12 days. The median time for gastrointestinal recovery was 5 days. One-fifth of patients (11, 19.7%) required an extended stay in the inten- sive care unit. The most common grades 3 and 4 complications were hypocalcaemia 32.1%, hypokalaemia 32.1%, anaemia 21.4% and thrombocytopenia 7.1%. Major morbidity requiring surgical intervention occurred in 8.9% of patients. The 60-day operative mortality was 1.8%. At a median follow-up of 16 months, 7.1% developed peritoneal recurrence, 8.9% had systemic recurrence and 7.1% succumbed to the disease. Patients with platinum-resistant ovarian carcinomas had more peritoneal recurrence (3.6%). CONCLUSION: In patients with PSM, surgical cytoreduction and HIPEC is feasible and potentially beneficial. It can be done with low mortality and acceptable morbidity. It requires a dedicated team of surgeons, anaesthetists and intensivists and proper infrastructure.

SYNTHESIS AND ANTIINFLAMMATORY ACTIVITY OF SOME IMIDAZO[2,1-b][1,3,4]THIADIAZOLE DERIVATIVES.

A number of imidazo[2,1-b][1,3,4]thiadiazole derivatives having alkyl and aryl moieties attached to positions 2 and 6 of imidazo[2,1-b][1,3,4]thiadiazole nucleus, respectively, were prepared and characterized by IR, NMR and mass spectroscopy. Antiinflammatory activity was evaluated by carrageenan-induced rat paw edema assay. By 5th hours, all compounds demonstrated anti-inflammatory activity similar or higher than that of standard NSAID, ibuprofen.

Estrogen receptor mutations and their role in breast cancer progression.

Endocrine therapy is the mainstay of treatment in estrogen receptor-positive breast cancers and significantly reduces disease recurrence and breast cancer-related mortality. However, acquired resistance to therapy has been noted in nearly one-third of women treated with tamoxifen and other endocrine therapies. Mutations in the estrogen receptor have long been speculated to play a role in endocrine therapy resistance but have been rarely detected. However, recent studies utilizing next-generation sequencing on estrogen receptor-positive, metastatic clinical samples have revealed that recurrent ESR1 mutations are far more frequent than previously thought and may play an important role in acquired endocrine therapy resistance. Here we review recent advances in detection and characterization of ESR1 mutations in advanced, endocrine therapy-resistant breast cancers.

Evaluation of efficacy of different gingival displacement materials on gingival sulcus width.

AIM: The purpose of the present in vivo study was to measure the efficacy of different gingival displacement materials in achieving gingival tissue displacement and to compare the efficacy of Expasyl displacement paste (Pierre Rolland, France) and gingival displacement cord for gingival displacement. MATERIALS AND METHODS: Sixteen subjects were included in the study. Premolars were prepared to receive full veneer crown, gingival displacement was carried using gingival retraction cord and gingival displacement paste. Impression of the gingival sulcus was made. Sulcus width after displacement was measured under magnification. RESULTS: The mean displacement value of sulcus width was 0.21 ± 0.01 mm for the gingival retraction cord and 0.26 ± 0.02 mm for the gingival displacement paste. 'F' test was used for statistical analysis. Difference among the two test agents was statistically significant (p < 0.01). CONCLUSION: Gingival displacement paste showed better response in achieving horizontal displacement of the gingival sulcus than gingival retraction cord. CLINICAL SIGNIFICANCE: Gingival displacement helps in recording the unprepared tooth surface adjacent to the finish line in the impression being made, thereby helping a better marginal adaptation and emergence profile in the extracoronal restoration.

On the possibility of estimating myocardial fiber architecture from cardiac strains.

The myocardium is composed of a complex network of contractile myofibers that are organized in such a way as to produce efficient contraction and relaxation of the heart. The myofiber architecture in the myocardium is a key determinant of cardiac motion and the global or organ-level function of the heart. Reports of architectural remodeling in cardiac diseases, such as pulmonary hypertension and myocardial infarction, potentially contributing to cardiac dysfunction call for the inclusion of an architectural marker for an improved assessment of cardiac function. However, the in-vivo quantification of three-dimensional myo-architecture has proven challenging. In this work, we examine the sensitivity of cardiac strains to varying myofiber orientation using a multiscale finite-element model of the LV. Additionally, we present an inverse modeling approach to predict the myocardium fiber structure from cardiac strains. Our results indicate a strong correlation between fiber orientation and LV kinematics, corroborating that the fiber structure is a principal determinant of LV contractile behavior. Our inverse model was capable of accurately predicting the myocardial fiber range and regional fiber angles from strain measures. A concrete understanding of the link between LV myofiber structure and motion, and the development of non-invasive and feasible means of characterizing the myocardium architecture is expected to lead to advanced LV functional metrics and improved prognostic assessment of structural heart disease.

Towards precision radiation oncology: endocrine therapy response as a biomarker for personalization of breast radiotherapy.

Targeted therapies, such as endocrine therapies (ET), can exert selective pressure on cancer cells and promote adaptations that confer treatment resistance. In this study, we show that ET resistance in breast cancer drives radiation resistance through reprogramming of DNA repair pathways. We also show that pharmacological bromodomain and extraterminal domain inhibition reverses pathological DNA repair reprogramming in ET-resistant breast tumors and overcomes resistance to radiation therapy.

Role of nanocellulose in industrial and pharmaceutical sectors - A review.

Lignocellulosic biomass from agricultural residues serves as the critical component to replace synthetic polymeric materials in the coming future. Agricultural residues can be used to obtain cellulose by delignification followed by bleaching. Further, cellulose is converted into nanocellulose by various methods. Nanocellulose is used in multiple pharmaceutical applications as a polymer in hydrogels, transdermal drug delivery systems, aerogels, wound healing dressing materials, as superdisintegrants in fast dissolving tablets, emulgel, microparticles, gels, foams, thickening agents, stabilizers, cosmetics, medical implants, tissue engineering, liposomes, food and composites, etc. This review provides detailed knowledge about the nature of nanocellulose regarding its high surface area, high polymerization, loading, and binding capacity of hydrophilic and hydrophobic active pharmaceutical ingredients and significance of various applications of nanocellulose. Biocompatible and non-toxic, it makes it an ideal material for applications in the biomedical field. A significant advantage is a biocompatibility, which is non-toxic for many biomedical applications.

Targeting radioresistance and replication fork stability in prostate cancer.

The bromodomain and extraterminal (BET) family of chromatin reader proteins bind to acetylated histones and regulate gene expression. The development of BET inhibitors (BETi) has expanded our knowledge of BET protein function beyond transcriptional regulation and has ushered several prostate cancer (PCa) clinical trials. However, BETi as a single agent is not associated with antitumor activity in patients with castration-resistant prostate cancer (CRPC). We hypothesized novel combinatorial strategies are likely to enhance the efficacy of BETi. By using PCa patient-derived explants and xenograft models, we show that BETi treatment enhanced the efficacy of radiation therapy (RT) and overcame radioresistance. Mechanistically, BETi potentiated the activity of RT by blocking DNA repair. We also report a synergistic relationship between BETi and topoisomerase I (TOP1) inhibitors (TOP1i). We show that the BETi OTX015 synergized with the new class of synthetic noncamptothecin TOP1i, LMP400 (indotecan), to block tumor growth in aggressive CRPC xenograft models. Mechanistically, BETi potentiated the antitumor activity of TOP1i by disrupting replication fork stability. Longitudinal analysis of patient tumors indicated that TOP1 transcript abundance increased as patients progressed from hormone-sensitive prostate cancer to CRPC. TOP1 was highly expressed in metastatic CRPC, and its expression correlated with the expression of BET family genes. These studies open new avenues for the rational combinatorial treatment of aggressive PCa.

Targeting ESR1 mutation-induced transcriptional addiction in breast cancer with BET inhibition.

Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is associated with development of resistance to most endocrine therapies used to treat breast cancer. Employing a high-throughput screen of nearly 1,200 Federal Drug Administration-approved (FDA-approved) drugs, we show that OTX015, a bromodomain and extraterminal domain (BET) inhibitor, is one of the top suppressors of ESR1 mutant cell growth. OTX015 was more efficacious than fulvestrant, a selective ER degrader, in inhibiting ESR1 mutant xenograft growth. When combined with abemaciclib, a CDK4/6 inhibitor, OTX015 induced more potent tumor regression than current standard-of-care treatment of abemaciclib + fulvestrant. OTX015 has preferential activity against Y537S mutant breast cancer cells and blocks their clonal selection in competition studies with WT cells. Thus, BET inhibition has the potential to both prevent and overcome ESR1 mutant-induced endocrine therapy resistance in breast cancer.

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs.

The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 µM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 µM) or latanoprost (IC(50)=0.48±0.15 µM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 µM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.

Comparison of Perinatal and Maternal Outcomes in Borderline Versus Normal Amniotic Fluid Index in a Tertiary Care Center in Odisha: An Observational Prospective Study.

Background Amniotic fluid is a protective fluid in the amniotic sac of a gravid uterus that serves many crucial functions by becoming part of an indicator of a functioning fetoplacental unit during the intrauterine life of a fetus. The most commonly used method for measuring amniotic fluid is the amniotic fluid index (AFI). In this study, we aimed to investigate the perinatal and maternal outcomes in borderline AFI versus normal AFI. Methodology This observational prospective study included 200 pregnant women who were admitted to Pradyumna Bal Memorial Hospital, Bhubaneswar from September 2019 to February 2021. Women with singleton pregnancy in their third trimester were enrolled in this study after applying inclusion and exclusion criteria. Of the included women, 100 were cases with borderline AFI, and 100 were control with normal AFI. Fetal and maternal outcomes were compared between the two groups. Data analysis was done using SPSS version 23 (IBM Corp., Armonk, NY, USA). Results Maternal outcomes such as preterm delivery, meconium-stained liquor, and lower segment cesarean section in women with borderline AFI were significantly higher (p ≤ 0.001). The borderline AFI group had a higher rate of perinatal complications such as Apgar score of <7 (p = 0.001), respiratory distress syndrome (p = 0.001), neonatal intensive care unit admission (p <0.001), intrauterine growth restriction (p < 0.001), and low birth weight (p < 0.001). Conclusions The borderline AFI group was associated with adverse perinatal and maternal outcomes which were significantly higher in this group compared to the control group. Therefore, patients with borderline AFI should be monitored carefully during the antepartum and intrapartum period.

Chordoid glioma: a rare old foe but a new pathological and radiological presentation.

Chordoid glioma (CG) is a rare WHO Grade II neoplasm of the anterior third ventricle. We report two cases of CG with new presentation in terms of histopathology and location: a case of CG with osseous metaplasia evident on imaging, and another CG, unusually located in the posterior portion of the third ventricle.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Posttraumatic retroclival acute subdural hematoma: report of two cases and review of literature.

Traumatic retroclival hematomas are uncommon lesions usually associated with significant trauma. Majority of the reported hematomas are epidural; and in the pediatric population. Retroclival acute subdural hematomas (RSDH) are very rare, with only two previous cases reported in English literature. An 18-year-old man presented with headache and no deficits following an accident. Computer tomography (CT) scan and magnetic resonance imaging (MRI) showed an acute RSDH extending into the spinal subdural space. He developed bilateral sixth nerve palsies, with symptoms of raised intracranial pressure within the next 24 hours. He underwent evacuation of hematoma with a good outcome. Another 19-year-old man presented with neck pain following a fall from a moving bus. He had no neurological deficits. CT scan showed a RSDH extending across the craniovertebral junction. He was managed conservatively with good outcome.

HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERß downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

1-Arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones as leads for developing cytotoxins and anticonvulsants.

Various substituted 1-arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones 3a-h, 1-benzyl-2,3-dioxo-2,3-dihydroindole N(4)-aryl thiosemicarbazones 4a-i and 1-benzyl-2,3-dioxy-2,3-dihydroindole N(4)-cyclohexylthiocarbazone 5 were synthesized. All of these compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Nearly 40% of these compounds possess low micromolar IC(50) values and some are either more potent than, or equipotent with, melphalan. Various correlations between the structures of these compounds and cytotoxic potencies were obtained which included the use of QSAR and molecular modeling techniques. Representative compounds displayed anticonvulsant properties in rats and were well tolerated by these animals. The encouraging biodata noted affords adequate rationale for outlining guidelines for further development of these molecular scaffolds.